Prof Susanna Hourani

Professor Susanna Hourani


Emeritus Professor of Pharmacology

Biography

Research interests

My research is in the field of adenosine and adenine nucleotides: their receptors, their effects and their physiological and pathological roles. They are important in platelet function, the control of the cardiovascular and gastrointestinal systems and in the brain. My research has been funded by The Wellcome Trust, The British Heart Foundation and GlaxoSmithKline.

Teaching

I teach pharmacology to both undergraduate and postgraduate students, focussing mainly on the effects of drugs outside the central nervous system.

Affiliations

Fellow of the British Pharmacological Society

Fellow of the Society of Biology

Member of the Biochemical Society

My publications

Publications

K Belchamber, DA Hall, SMO Hourani (2014)Smoking Enhances the Proinflammatory Effects of Nucleotides on Cytokine Release from Human Lung, In: PLOS ONE9(6)ARTN e9971 PUBLIC LIBRARY SCIENCE
J Nicholls, SMO Hourani, JM Hall (1999)Characterisation of receptors mediating vasomotor effects of adenosine analogues in hamster cheek pouch, In: BRITISH JOURNAL OF PHARMACOLOGY126pp. U103-U103 STOCKTON PRESS
SMO HOURANI, LA WELFORD, GD LOIZOU, NJ CUSAK (1988)ADENOSINE 5'-(2-FLUORODIPHOSPHATE) IS A SELECTIVE AGONIST AT P2-PURINOCEPTORS MEDIATING RELAXATION OF SMOOTH-MUSCLE, In: EUROPEAN JOURNAL OF PHARMACOLOGY147(1)pp. 131-136 ELSEVIER SCIENCE BV
NJ Cusack, SMO Hourani (2000)Platelet P2 receptors: from curiosity to clinical targets, In: JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM81(1-3)pp. 37-43 ELSEVIER SCIENCE BV
P Zanos, SR Wright, P Georgiou, JH Yoo, SM Hourani, I Kitchen, R Winsky-Sommerer, A Bailey, C Ledent (2014)Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A receptor-independent mechanism, In: Pharmacology Biochemistry and Behavior119pp. 72-79

There is mounting evidence that the neuropeptide oxytocin is a possible candidate for the treatment of drug addiction. Oxytocin was shown to reduce methamphetamine self-administration, conditioned place-preference, hyperactivity and reinstatement in rodents, highlighting its potential for the management of methamphetamine addiction. Thus, we hypothesised that the central endogenous oxytocinergic system is dysregulated following chronic methamphetamine administration. We tested this hypothesis by examining the effect of chronic methamphetamine administration on oxytocin receptor density in mice brains with the use of quantitative receptor autoradiographic binding. Saline (4 ml/kg/day, i.p.) or methamphetamine (1 mg/kg/day, i.p.) was administered daily for 10 days to male, CD1 mice. Quantitative autoradiographic mapping of oxytocin receptors was carried out with the use of [I]-vasotocin in brain sections of these animals. Chronic methamphetamine administration induced a region specific upregulation of oxytocin receptor density in the amygdala and hypothalamus, but not in the nucleus accumbens and caudate putamen. As there is evidence suggesting an involvement of central adenosine A receptors on central endogenous oxytocinergic function, we investigated whether these methamphetamine-induced oxytocinergic neuroadaptations are mediated via an A receptor-dependent mechanism. To test this hypothesis, autoradiographic oxytocin receptor binding was carried out in brain sections of male CD1 mice lacking A receptors which were chronically treated with methamphetamine (1 mg/kg/day, i.p. for 10 days) or saline. Similar to wild-type animals, chronic methamphetamine administration induced a region-specific upregulation of oxytocin receptor binding in the amygdala and hypothalamus of A receptor knockout mice and no genotype effect was observed. These results indicate that chronic methamphetamine use can induce profound neuroadaptations of the oxytocinergic receptor system in brain regions associated with stress, emotionality and social bonding and that these neuroadaptations are independent on the presence of A receptors. These results may at least partly explain some of the behavioural consequences of chronic methamphetamine use. © 2013 Elsevier Inc. All rights reserved.

HS Park, SMO Hourani (1999)Different effects of adenine nucleotide analogues on the responses mediated by adenosine 5 ' diphosphate (ADP) receptors on human platelets, In: BRITISH JOURNAL OF PHARMACOLOGY126pp. U103-U103 STOCKTON PRESS
A Metaxas, R Al-Hasani, P Farshim, K Tubby, A Berwick, C Ledent, S Hourani, I Kitchen, A Bailey (2013)Genetic deletion of the adenosine A2A receptor prevents nicotine-induced upregulation of α7, but not α4β2* nicotinic acetylcholine receptor binding in the brain., In: Neuropharmacology71pp. 228-236

Considerable evidence indicates that adenosine A2A receptors (A2ARs) modulate cholinergic neurotransmission, nicotinic acetylcholine receptor (nAChR) function, and nicotine-induced behavioural effects. To explore the interaction between A2A and nAChRs, we examined if the complete genetic deletion of adenosine A2ARs in mice induces compensatory alterations in the binding of different nAChR subtypes, and whether the long-term effects of nicotine on nAChR regulation are altered in the absence of the A2AR gene. Quantitative autoradiography was used to measure cytisine-sensitive [(125)I]epibatidine and [(125)I]α-bungarotoxin binding to α4β2* and α7 nAChRs, respectively, in brain sections of drug-naïve (n = 6) or nicotine treated (n = 5-7), wild-type and adenosine A2AR knockout mice. Saline or nicotine (7.8 mg/kg/day; free-base weight) were administered to male CD1 mice via subcutaneous osmotic minipumps for a period of 14 days. Blood plasma levels of nicotine and cotinine were measured at the end of treatment. There were no compensatory developmental alterations in nAChR subtype distribution or density in drug-naïve A2AR knockout mice. In nicotine treated wild-type mice, both α4β2* and α7 nAChR binding sites were increased compared with saline treated controls. The genetic ablation of adenosine A2ARs prevented nicotine-induced upregulation of α7 nAChRs, without affecting α4β2* receptor upregulation. This selective effect was observed at plasma levels of nicotine that were within the range reported for smokers (10-50 ng ml(-1)). Our data highlight the involvement of adenosine A2ARs in the mechanisms of nicotine-induced α7 nAChR upregulation, and identify A2ARs as novel pharmacological targets for modulating the long-term effects of nicotine on α7 receptors.

ML Tickner, DJ Lamb, AC Dreux, W El-Sankary, S Hourani, LJ Eales-Reynolds, GAA Ferns (2003)BCG immunisation impairs vascular relaxation and enhances atherosclerosis in the chronically hypercholesterolaemic rabbit, In: BRITISH JOURNAL OF PHARMACOLOGY140
DJ Prentice, MDW Kelly, C Ledent, SMO Hourani (2001)Effect of A(2A) adenosine receptor knockout on relaxant effects of adenosine and analogues in mouse isolated aorta., In: BRITISH JOURNAL OF PHARMACOLOGY134 NATURE PUBLISHING GROUP
SMO HOURANI, SJ BAILEY, J NICHOLLS, I KITCHEN (1991)DIRECT EFFECTS OF ADENYLYL 5'-(BETA,GAMMA-METHYLENE)DIPHOSPHONATE, A STABLE ATP ANALOG, ON RELAXANT P1-PURINOCEPTORS IN SMOOTH-MUSCLE, In: BRITISH JOURNAL OF PHARMACOLOGY104(3)pp. 685-690 STOCKTON PRESS
SMO Hourani, CJ Mackins, MDW Kelly, C Ledent, DJ Prentice (2001)Effect of A(2A) adenosine receptor knock-out on inhibition by NECA and CGS21680 of KCl-induced contractions in murine vas deferens, In: BRITISH JOURNAL OF PHARMACOLOGY134 NATURE PUBLISHING GROUP
L Godfrey, A Morselli, P Bennion, GD Clarke, SMO Hourani, I Kitchen (2005)An investigation of binding sites for paracetamol in the mouse brain and spinal cord, In: EUROPEAN JOURNAL OF PHARMACOLOGY508(1-3)pp. 99-106 ELSEVIER SCIENCE BV
DJ Lamb, ML Tickner, SMO Hourani, GAA Ferns (2005)Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis, In: INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY86(4)pp. 247-255 BLACKWELL PUBLISHING
SJ BAILEY, SMO HOURANI (1990)A STUDY OF THE PURINOCEPTORS MEDIATING CONTRACTION IN THE RAT COLON, In: BRITISH JOURNAL OF PHARMACOLOGY100(4)pp. 753-756 STOCKTON PRESS
SJ BAILEY, SMO HOURANI (1995)EFFECTS OF SURAMIN ON CONTRACTIONS OF THE GUINEA-PIG VAS-DEFERENS INDUCED BY ANALOGS OF ADENOSINE 5'-TRIPHOSPHATE, In: BRITISH JOURNAL OF PHARMACOLOGY114(6)pp. 1125-1132 STOCKTON PRESS
D Lamb, M Tickner, W El-Sankary, S Hourani, LJ Reynolds, G Ferns (2002)Immunisation with bacillus Calmette-Guerin enhances aortic atherosclerosis in chronic low level hypercholesterolaemic rabbits, In: ATHEROSCLEROSIS: RISK FACTORS, DIAGNOSIS, AND TREATMENTpp. 463-466
J NICHOLLS, SMO HOURANI, I KITCHEN (1992)CHARACTERIZATION OF P1-PURINOCEPTORS ON RAT DUODENUM AND URINARY-BLADDER, In: BRITISH JOURNAL OF PHARMACOLOGY105(3)pp. 639-642 STOCKTON PRESS
MDW Kelly, C Ledent, I Kitchen, SMO Hourani (2003)Characterization of [H-3]-ZM 241385 binding in wildtype and A(2A) knockout mouse brain, In: BRITISH JOURNAL OF PHARMACOLOGY140
SMO Hourani (2001)Discovery and recognition of purine receptor subtypes on platelets, In: DRUG DEVELOPMENT RESEARCH52(1-2)pp. 140-149
J NICHOLLS, SMO HOURANI, I KITCHEN (1990)THE ONTOGENY OF PURINOCEPTORS IN RAT URINARY-BLADDER AND DUODENUM, In: BRITISH JOURNAL OF PHARMACOLOGY100(4)pp. 874-878 STOCKTON PRESS
L Godfrey, SMO Hourani, I Kitchen (2003)Quantitative autoradiography of [H-3]paracetamol binding in the mouse brain, In: BRITISH JOURNAL OF PHARMACOLOGY140
SMO HOURANI, NJ CUSACK (1991)PHARMACOLOGICAL RECEPTORS ON BLOOD-PLATELETS, In: PHARMACOLOGICAL REVIEWS43(3)pp. 243-298 WILLIAMS & WILKINS
L Wells, J Opacka-Juffry, D Fisher, C Ledent, S Hourani, I Kitchen (2011)In vivo dopaminergic and behavioural responses to acute cocaine are altered in adenosine A(2A) receptor knockout mice., In: Synapse66pp. 382-390 Wiley

Adenosine, acting on A(2A) adenosine receptors, regulates addictive processes induced by drugs of abuse. The present study investigates the role of A(2A) adenosine receptors in neurochemical and behavioural responses to an acute cocaine challenge. Changes in the extracellular levels of dopamine in the nucleus accumbens of mice lacking A(2A) adenosine receptors and wild type littermates after an acute cocaine (20mg/kg) administration were evaluated by in vivo microdialysis studies. Locomotor effects induced by cocaine were measured during the microdialysis procedure. Cocaine-evoked increases in extracellular dopamine were not sustained in mice lacking A(2A) receptors in comparison to wild-type mice (P

A Bailey, HMB Lesscher, MDW Kelly, L Davis, C Ledent, SMO Hourani, I Kitchen (2003)Morphine withdrawal in A(2A) adenosine receptor knockout mice, In: BRITISH JOURNAL OF PHARMACOLOGY140
L Godfrey, I Bailey, NJ Toms, GD Clarke, I Kitchen, SMO Hourani (2007)Paracetamol inhibits nitric oxide synthesis in murine spinal cord slices, In: EUR J PHARMACOL562(1-2)pp. 68-71 ELSEVIER SCIENCE BV

Paracetamol is an effective analgesic but its mechanism of action is unclear. We investigated the effect of paracetamol and the analgesic adjuvant caffeine on the activity of NO synthase in mouse spinal cord and cerebellar slices in vitro, by measuring the conversion of [3H]arginine to [3H]citrulline. Paracetamol (100 μM) had no effect on NO synthase activity in cerebellum, but in the spinal cord both paracetamol (100 μM) and caffeine (30 μM) attenuated glutamate (5 mM)-induced [3H]citrulline production and in combination they abolished it. In conclusion paracetamol inhibits spinal cord NO synthesis and this may be related to its analgesic effects.

SMO HOURANI, GD LOIZOU, NJ CUSACK (1986)PHARMACOLOGICAL EFFECTS OF L-AMP-PCP ON ATP RECEPTORS IN SMOOTH-MUSCLE, In: EUROPEAN JOURNAL OF PHARMACOLOGY131(1)pp. 99-103 ELSEVIER SCIENCE BV
MJ Hussey, GD Clarke, C Ledent, I Kitchen, SM Hourani (2012)Deletion of the adenosine A(2A) receptor in mice enhances spinal cord neurochemical responses to an inflammatory nociceptive stimulus., In: Neurosci Lett506(2)pp. 198-202 Elsevier

Knockout mice lacking the adenosine A(2A) receptor are less sensitive to nociceptive stimuli, and this may be due to the presence of pronociceptive A(2A) receptors on sensory nerves. In support of this hypothesis, we have recently shown that in A(2A) receptor knockout mice there are marked reductions in the changes of two markers of spinal cord neuronal activity, [(3)H]MK801 binding to NMDA receptors and uptake of [(14)C]-2-deoxyglucose, in response to formalin injection. We now report that following a more prolonged inflammatory stimulus, consisting of intraplantar injections of PGE(2) and paw pressure, there was in contrast an increase in [(3)H]MK801 binding and [(14)C]-2-deoxyglucose uptake in the spinal cords of the A(2A) receptor knockout mice which was much greater than in the wild-type mice. This increase suggests that when there is a pronounced inflammatory component to the stimulus, loss of inhibitory A(2A) receptors on inflammatory cells outweighs the loss of pronociceptive A(2A) receptors on peripheral nerves so that overall there is an increase in nociceptive signalling. This implies that although A(2A) antagonists have antinociceptive effects they may have only limited use as analgesics in chronic inflammatory pain.

NJ CUSACK, SMO HOURANI, GD LOIZOU, LA WELFORD (1987)PHARMACOLOGICAL EFFECTS OF ISOPOLAR PHOSPHONATE ANALOGS OF ATP ON P-2-PURINOCEPTORS IN GUINEA-PIG TAENIA-COLI AND URINARY-BLADDER, In: BRITISH JOURNAL OF PHARMACOLOGY90(4)pp. 791-795 STOCKTON PRESS
SMO HOURANI, SJ BAILEY, J NICHOLLS, I KITCHEN (1991)AMPPCP ACTS VIA P1-RECEPTORS AND NOT P2-RECEPTORS IN SOME ISOLATED SMOOTH-MUSCLE PREPARATIONS, In: NUCLEOSIDES & NUCLEOTIDES10(5)pp. 1203-1205
A Bailey, C Ledent, MDW Kelly, I Kitchen, SMO Hourani (2002)Changes in opioid systems in A(2A) receptor knockout mice, In: DRUG DEVELOPMENT RESEARCH56(4)pp. 562-562
A Bailey, C Ledent, M Kelly, SMO Hourani, I Kitchen (2002)Changes in spinal delta and kappa opioid systems in mice deficient in the A(2A) receptor gene, In: JOURNAL OF NEUROSCIENCE22(21)pp. 9210-9220 SOC NEUROSCIENCE
M Kelly, A Bailey, C Ledent, I Kitchen, S Hourani (2004)Characterization of [H-3]ZM 241385 binding in wild-type and adenosine A(2A) receptor knockout mice, In: EUROPEAN JOURNAL OF PHARMACOLOGY504(1-2)pp. 55-59 ELSEVIER SCIENCE BV
HS Park, JP Tennant, GF Waktolla, S Sarkardei, GEN Kass, SMO Hourani (1998)Effects of adenosine 3 '-phosphate 5 '-phosphosulfate on P2 receptors in platelets and smooth muscle preparations, In: DRUG DEVELOPMENT RESEARCH45(2)pp. 67-73 WILEY-LISS
MJ Hussey, GD Clarke, C Ledent, SMO Hourani, I Kitchen (2007)Reduced response to the formalin test and lowered spinal NMDA glutamate receptor binding in adenosine A(2A) receptor knockout mice, In: PAIN129(3)pp. 287-294 ELSEVIER SCIENCE BV
L Godfrey, L Yan, GD Clarke, C Ledent, I Kitchen, SMO Hourani (2006)Modulation of paracetamol antinociception by caffeine and by selective adenosine A(2) receptor antagonists in mice, In: EUR J PHARMACOL531(1-3)pp. 80-86 ELSEVIER SCIENCE BV

This study investigated the involvement of adenosine receptors in the interaction between paracetamol and caffeine in mice, using the adenosine A2A receptor antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261) and the adenosine A2B receptor antagonist 1-propyl-8-p-sulfophenylxanthine (PSB1115), in the tail immersion and hot-plate tests. Paracetamol (10–200 mg/kg) was antinociceptive in both tests, but, in contrast to previous studies, caffeine (10 mg/kg) was pronociceptive in the tail immersion test, and reduced the effects of paracetamol in both tests. SCH58261 (3 mg/kg) was antinociceptive in both tests and in its presence paracetamol (50 mg/kg) had no further effect. PSB1115 (10 mg/kg) had little effect alone but potentiated the effect of paracetamol (50 mg/kg) in the hot-plate test and abolished it in the tail immersion test. These results suggest that adenosine A2B receptors may be involved in the action of paracetamol in a pathway-dependent manner, and also support the existence of pronociceptive adenosine A2A receptors

P Georgiou, P Zanos, J-A Garcia-Carmona, S Hourani, I Kitchen, BL Kieffer, M-L Laorden, A Bailey (2015)The oxytocin analogue carbetocin prevents priming-induced reinstatement of morphine-seeking: Involvement of dopaminergic, noradrenergic and MOPr systems, In: EUROPEAN NEUROPSYCHOPHARMACOLOGY25(12)pp. 2459-2464 ELSEVIER SCIENCE BV
SR Wright, P Zanos, P Georgiou, JH Yoo, C Ledent, SM Hourani, I Kitchen, R Winsky-Sommerer, A Bailey (2015)A critical role of striatal A2A R-mGlu5 R interactions in modulating the psychomotor and drug-seeking effects of methamphetamine., In: ADDICT BIOL WILEY-BLACKWELL PUBLISHING, INC

Addiction to psychostimulants is a major public health problem with no available treatment. Adenosine A2A receptors (A2A R) co-localize with metabotropic glutamate 5 receptors (mGlu5 R) in the striatum and functionally interact to modulate behaviours induced by addictive substances, such as alcohol. Using genetic and pharmacological antagonism of A2A R in mice, we investigated whether A2A R-mGlu5 R interaction can regulate the locomotor, stereotypic and drug-seeking effect of methamphetamine and cocaine, two drugs that exhibit distinct mechanism of action. Genetic deletion of A2A R, as well as combined administration of sub-threshold doses of the selective A2A R antagonist (SCH 58261, 0.01 mg/kg, i.p.) with the mGlu5 R antagonist, 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (0.01 mg/kg, i.p.), prevented methamphetamine- but not cocaine-induced hyperactivity and stereotypic rearing behaviour. This drug combination also prevented methamphetamine-rewarding effects in a conditioned-place preference paradigm. Moreover, mGlu5 R binding was reduced in the nucleus accumbens core of A2A R knockout (KO) mice supporting an interaction between these receptors in a brain region crucial in mediating addiction processes. Chronic methamphetamine, but not cocaine administration, resulted in a significant increase in striatal mGlu5 R binding in wild-type mice, which was absent in the A2A R KO mice. These data are in support of a critical role of striatal A2A R-mGlu5 R functional interaction in mediating the ambulatory, stereotypic and reinforcing effects of methamphetamine but not cocaine-induced hyperlocomotion or stereotypy. The present study highlights a distinct and selective mechanistic role for this receptor interaction in regulating methamphetamine-induced behaviours and suggests that combined antagonism of A2A R and mGlu5 R may represent a novel therapy for methamphetamine addiction.

A Castane, L Wells, G Soria, S Hourani, C Ledent, I Kitchen, J Opacka-Juffry, R Maldonado, O Valverde (2008)Behavioural and biochemical responses to morphine associated with its motivational properties are altered in adenosine A(2A) receptor knockout mice, In: BRIT J PHARMACOL155(5)pp. 757-766 NATURE PUBLISHING GROUP

Background and purpose. Purinergic system through the A2A adenosine receptor regulates addiction induced by different drugs of abuse. The aim of the present study was to investigate the specific role of A2A adenosine receptors in behavioral and neurochemical morphine responses related to its addictive properties. Experimental approach. Mice lacking A2A adenosine receptors and wild type littermates were used to evaluate behavioral responses induced by morphine. Antinociception was assessed using the tail-immersion and the hot-plate tests. Place conditioning paradigms were used to evaluate the rewarding effects of morphine and the dysphoric responses of morphine withdrawal. Microdialysis studies were carried out to evaluate changes in the extracellular levels of dopamine in the nucleus accumbens of A2A knockout mice after morphine administration. Key results. The acute administration of morphine induced a similar enhancement of locomotor activity and antinociceptive responses in both genotypes. However, the rewarding effects induced by morphine were completely blocked in A2A knockout mice. Besides, naloxone did not induce place aversion in animals lacking the A2A adenosine receptors. Conclusions and implications. Our findings demonstrate the relevant role played by A2A adenosine receptors in the addictive properties of morphine. Both, rewarding and aversive effects associated to abstinence were abolished in A2A knockout mice, supporting a differential role of the A2A adenosine receptor in somatic and motivational effects of morphine addiction. This study provides evidence about the role of A2A adenosine receptor as a general modulator of the addictive phenomenon.

P Georgiou, P Zanos, J-A Garcia-Carmona, S Hourani, I Kitchen, M-L Laorden, A Bailey (2016)Methamphetamine abstinence induces changes in mu-opioid receptor, oxytocin and CRF systems: Association with an anxiogenic phenotype, In: NEUROPHARMACOLOGY105pp. 520-532 PERGAMON-ELSEVIER SCIENCE LTD
P Zanos, P Georgiou, LR Gonzalez, S Hourani, Y Chen, I Kitchen, BL Kieffer, R Winsky-Sommerer, A Bailey (2016)Emotional Impairment and Persistent Upregulation of mGlu(5) Receptor following Morphine Abstinence: Implications of an mGlu(5)-MOPr Interaction, In: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY19(7) OXFORD UNIV PRESS
JA PEACHEY, VR BROWNHILL, SMO HOURANI, I KITCHEN (1995)THE ONTOGENY OF ADENOSINE RECEPTOR SUBTYPES IN THE RAT VAS-DEFERENS, In: BRITISH JOURNAL OF PHARMACOLOGY115pp. P143-P143 STOCKTON PRESS
DJ PRENTICE, SMO HOURANI (1995)NECA AND R-PIA ACTIVATE DISTINCT SITES TO CAUSE RELAXATION OF THE ISOLATED RAT AORTA, In: BRITISH JOURNAL OF PHARMACOLOGY115pp. P64-P64 STOCKTON PRESS
JP Tennant, EJ Samuel, SMO Hourani (1997)Ectonucleotidase activity in the prostatic and epididymal portions of the guinea-pig vasdeferens, In: BRITISH JOURNAL OF PHARMACOLOGY122pp. P146-P146 STOCKTON PRESS
A Bailey, RM Hawkins, SMO Hourani, I Kitchen (2003)Quantitative autoradiography of adenosine receptors in brains of chronic naltrexone-treated mice, In: BRITISH JOURNAL OF PHARMACOLOGY139(6)pp. 1187-1195 NATURE PUBLISHING GROUP
DJ Prentice, SMO Hourani (1997)Information in agonist curve shape for receptor classification, In: RECEPTOR CLASSIFICATION812pp. 234-235
MG COLLIS, SMO HOURANI (1993)ADENOSINE RECEPTOR SUBTYPES, In: TRENDS IN PHARMACOLOGICAL SCIENCES14(10)pp. 360-366 ELSEVIER SCI LTD
MR Boarder, SMO Hourani (1998)The regulation of vascular function by P2 receptors: multiple sites and multiple receptors, In: TRENDS IN PHARMACOLOGICAL SCIENCES19(3)pp. 99-107 ELSEVIER SCI LTD
JA PEACHEY, SMO HOURANI, I KITCHEN (1994)ADENOSINE-A(1) BINDING-SITES IN RAT SMOOTH-MUSCLE PREPARATIONS, In: BRITISH JOURNAL OF PHARMACOLOGY111pp. P323-P323 STOCKTON PRESS
D Ribe, D Sawbridge, S Thakur, M Hussey, C Ledent, I Kitchen, S Hourani, J-M Li (2008)Adenosine A(2A) receptor signaling regulation of cardiac NADPH oxidase activity, In: FREE RADICAL BIOLOGY AND MEDICINE44(7)pp. 1433-1442 ELSEVIER SCIENCE INC
J Nicholls, SMO Hourani (1997)Characterization of adenosine receptors on rat ileum, ileal longitudinal muscle and muscularis mucosae, In: EUROPEAN JOURNAL OF PHARMACOLOGY338(2)pp. 143-150 ELSEVIER SCIENCE BV
SMO Hourani (1999)Postnatal development of purinoceptors in rat visceral smooth muscle preparations, In: GENERAL PHARMACOLOGY32(1)pp. 3-7 PERGAMON-ELSEVIER SCIENCE LTD
SR Smith, N Pochani, R Al-Hasani, S Hourani, L Wells, I Kitchen, A Bailey (2011)Metabotropic mGluR5-and adenosine A(2A)-receptor interactions in opioid addiction, In: PHARMACOLOGICAL REPORTS63(1)pp. 225-225 POLISH ACAD SCIENCES INST PHARMACOLOGY
SMO Hourani (1996)Purinoceptors and platelet aggregation, In: JOURNAL OF AUTONOMIC PHARMACOLOGY16(6)pp. 349-352 BLACKWELL SCIENCE LTD
SMO Hourani, NC Smith, JJ Nettell, JM Hall (1997)Relaxation of the ovine isolated iris sphincter by adenosine receptor agonists: Lack of effect of adenosine A(1) and A(2) receptor antagonists, In: EUROPEAN JOURNAL OF PHARMACOLOGY334(1)pp. 95-98 ELSEVIER SCIENCE BV
JA Peachey, SMO Hourani, I Kitchen (1996)Differential development of adenosine A(1) and A(2b) receptors in the rat duodenum, In: BRITISH JOURNAL OF PHARMACOLOGY119(5)pp. 949-958 STOCKTON PRESS
DJ Prentice, SMO Hourani (1997)Adenosine analogues relax guinea-pig taenia caeci via an adenosine A(2B) receptor and a xanthine-resistant site, In: EUROPEAN JOURNAL OF PHARMACOLOGY323(1)pp. 103-106 ELSEVIER SCIENCE BV
D Lamb, M Tickner, A Dreux, W El-Sankary, S Hourani, LJ Eales-Reynolds, G Ferns (2003)BCG immunization is atherogenic in the chronically hypercholesterolaemic rabbit: Immune and vascular endothelial effects, In: ATHEROSCLEROSIS SUPPLEMENTS4(2)pp. 310-310
JA Peachey, VR Brownhill, SMO Hourani, I Kitchen (1996)The ontogenetic profiles of the pre- and postjunctional adenosine receptors in the rat vas deferens, In: BRITISH JOURNAL OF PHARMACOLOGY117(6)pp. 1105-1110 STOCKTON PRESS
A Bailey, L Davis, HMB Lesscher, MDW Kelly, C Ledent, SMO Hourani, I Kitchen (2004)Enhanced morphine withdrawal and mu-opioid receptor G-protein coupling in A(2A) adenosine receptor knockout ti ice, In: JOURNAL OF NEUROCHEMISTRY88(4)pp. 827-834 BLACKWELL PUBLISHING LTD
VR Brownhill, SMO Hourani, I Kitchen (1997)Ontogeny of P2-purinoceptors in the longitudinal muscle and muscularis mucosae of the rat isolated duodenum, In: BRITISH JOURNAL OF PHARMACOLOGY122(2)pp. 225-232 STOCKTON PRESS
P Georgiou, P Zanos, M Ehteramyan, S Hourani, I Kitchen, R Maldonado, A Bailey (2015)Differential regulation of mGlu(5)R and MOPr by priming- and cue-induced reinstatement of cocaine-seeking behaviour in mice, In: ADDICTION BIOLOGY20(5)pp. 902-912 WILEY-BLACKWELL
J Nicholls, VR Brownhill, SMO Hourani (1996)Characterization of P-1-purinoceptors on rat isolated duodenum longitudinal muscle and muscularis mucosae, In: BRITISH JOURNAL OF PHARMACOLOGY117(1)pp. 170-174 STOCKTON PRESS
DJ Prentice, SMO Hourani (2000)Characterisation of adenosine receptors mediating relaxation in hamster isolated aorta, In: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY362(4-5)pp. 427-434 SPRINGER-VERLAG
CR Johnson, SJ Charlton, SMO Hourani (1996)Responses of the longitudinal muscle and the muscularis mucosae of the rat duodenum to adenine and uracil nucleotides, In: BRITISH JOURNAL OF PHARMACOLOGY117(5)pp. 823-830 STOCKTON PRESS
VR Brownhill, SMO Hourani, I Kitchen (1996)Differential distribution of adenosine A(2) receptors in the epididymal and prostatic portions of the rat vas deferens, In: EUROPEAN JOURNAL OF PHARMACOLOGY303(1-2)pp. 87-90 ELSEVIER SCIENCE BV
SMO HOURANI, J NICHOLLS, BSS LEE, EJ HALFHIDE, I KITCHEN (1993)CHARACTERIZATION AND ONTOGENY OF P-1-PURINOCEPTORS ON RAT VAS-DEFERENS, In: BRITISH JOURNAL OF PHARMACOLOGY108(3)pp. 754-758 STOCKTON PRESS
VR Brownhill, SMO Hourani, I Kitchen (1996)Selective enhancement by an adenosine A(1) receptor agonist of agents inducing contraction of the rat vas deferens, In: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY353(5)pp. 499-504 SPRINGER VERLAG
JP Tennant, SMO Hourani (2000)Breakdown of extracellular ATP by the prostatic and epididymal ends of the guinea pig vas deferens, In: EUROPEAN JOURNAL OF PHARMACOLOGY387(1)pp. 107-109 ELSEVIER SCIENCE BV
CD Lewis, SMO Hourani (1997)Involvement of functional antagonism in the effects of adenosine antagonists and L-NAME in the rat isolated heart, In: GENERAL PHARMACOLOGY29(3)pp. 421-427 PERGAMON-ELSEVIER SCIENCE LTD
DJ Prentice, SL Payne, SMO Hourani (1997)Activation of two sites by adenosine receptor agonists to cause relaxation in rat isolated mesenteric artery, In: BRITISH JOURNAL OF PHARMACOLOGY122(7)pp. 1509-1515 STOCKTON PRESS
DJ Prentice, SMO Hourani (1996)Activation of multiple sites by adenosine analogues in the rat isolated aorta, In: BRITISH JOURNAL OF PHARMACOLOGY118(6)pp. 1509-1517 STOCKTON PRESS
SMO Hourani, DA Hall (1996)P2T purinoceptors: ADP receptors on platelets, In: P2 PURINOCEPTORS: LOCALIZATION, FUNCTION AND TRANSDUCTION MECHANISMS198pp. 53-70 JOHN WILEY & SONS LTD
VR Brownhill, SMO Hourani, I Kitchen (1996)Differential ontogeny of adenosine receptors in the longitudinal muscle and muscularis mucosae of the rat isolated duodenum, In: EUROPEAN JOURNAL OF PHARMACOLOGY317(2-3)pp. 321-328 ELSEVIER SCIENCE BV
S Ferre, I Diamond, SR Goldberg, L Yao, SMO Hourani, ZL Huang, Y Urade, I Kitchen (2007)Adenosine A(2A) receptors in ventral striatum, hypothalamus and nociceptive circuitry - Implications for drug addiction, sleep and pain, In: PROGRESS IN NEUROBIOLOGY83(5)pp. 332-347
SMO HOURANI, DA HALL, CJ NIEMAN (1992)EFFECTS OF THE P(2)-PURINOCEPTOR ANTAGONIST, SURAMIN, ON HUMAN PLATELET-AGGREGATION INDUCED BY ADENOSINE 5'-DIPHOSPHATE, In: BRITISH JOURNAL OF PHARMACOLOGY105(2)pp. 453-457 STOCKTON PRESS
DJ Lamb, ML Tickner, AC Dreux, W El-Sankary, SMO Hourani, LJ Eales-Reynolds, GAA Ferns (2004)Impairment of vascular function following BCG immunisation is associated with immune responses to HSP-60 in the cholesterol-fed rabbit, In: ATHEROSCLEROSIS172(1)pp. 13-20 ELSEVIER SCI IRELAND LTD

1 The aim of this study was to characterize the adenosine receptor mediating vasodilation in the microvasculature of the hamster cheek pouch in vivo. A range of adenosine agonists was used including N6-cyclopentyladenosine (CPA) (A1 agonist), 5'-N-ethylcarboxamidoadenosine (NECA) (non-selective), 2-chloroadenosine (2CADO) (non-selective), 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) (A2A agonist), N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IBMECA) (A3 agonist) and adenosine, as well as the adenosine antagonists 8-sulphophenyltheophylline (8-SPT) (A1/A2 antagonist), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (A1 antagonist) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) (A2A antagonist). 2 All the adenosine analogues used induced vasodilation at concentrations between 10 nm and 1 microm, and the potency order was NECA > CGS 21680 > 2CADO > CPA=IBMECA > adenosine, indicating an action at A2A receptors. 8-SPT (50 microm) antagonized vasodilator responses to NECA with an apparent pKB of 5.4, consistent with an action at A1 or A2 receptors and confirming that A3 receptors are not involved in this response. 3 DPCPX (10 nm) had no effect on vasodilation evoked by NECA, suggesting that this response was not mediated via A1 receptors, while ZM 241385 (10 nm) antagonized dilator responses to NECA with an apparent pKB of 8.9 consistent with an action via A2A receptors. 4 Overall these results suggest that adenosine A2A receptors mediate vasodilation in the hamster cheek pouch in vivo.

1 The aim of this study was to examine whether sodium nitroprusside (SNP)-induced relaxation of rat fundus longitudinal smooth muscle involves ryanodine-sensitive Ca2+ release. 2 SNP (300 nM-30 microM) elicited concentration-dependent relaxation of precontracted (1 microM carbachol) rat fundus, an effect almost abolished by the selective guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 microM). 3 SNP-mediated relaxations were almost abolished by 10 microM ryanodine. 4 SNP-mediated relaxations were also reduced by either 1 microM apamin (a selective small conductance Ca(2+)-sensitive K+ channel, SKCa, inhibitor) or the selective L-type Ca2+ channel inhibitor, nicardipine (3 microM). 5 SNP-induced relaxations were insensitive to 1 mM tetraethylammonium chloride (an inhibitor of large-conductance Ca(2+)-sensitive K+ channels) and 1 microM glibenclamide (an ATP-sensitive K+ channel inhibitor). 6 These data suggest that SNP-mediated fundus relaxation occurs via a cGMP-mediated and ryanodine-sensitive mechanism which requires, at least in part, SKCa and L-type Ca2+ channel activity.

SJ BAILEY, SMO HOURANI (1992)EFFECTS OF PURINES ON THE LONGITUDINAL MUSCLE OF THE RAT COLON, In: BRITISH JOURNAL OF PHARMACOLOGY105(4)pp. 885-892 STOCKTON PRESS
SJ BAILEY, D HICKMAN, SMO HOURANI (1992)CHARACTERIZATION OF THE P(1)-PURINOCEPTORS MEDIATING CONTRACTION OF THE RAT COLON MUSCULARIS MUCOSAE, In: BRITISH JOURNAL OF PHARMACOLOGY105(2)pp. 400-404 STOCKTON PRESS
SMO Hourani, K Boon, HM Fooks, DJ Prentice (2001)Role of cyclic nucleotides in vasodilations of the rat thoracic aorta induced by adenosine analogues, In: BRITISH JOURNAL OF PHARMACOLOGY133(6)pp. 833-840 NATURE PUBLISHING GROUP
JA PEACHEY, SMO HOURANI, I KITCHEN (1994)THE BINDING OF 1,3-[H-3]-DIPROPYL-8-CYCLOPENTYLXANTHINE TO ADENOSINE A(1) RECEPTORS IN RAT SMOOTH-MUSCLE PREPARATIONS, In: BRITISH JOURNAL OF PHARMACOLOGY113(4)pp. 1249-1256 STOCKTON PRESS
S Thakur, J Du, S Hourani, C Ledent, J-M Li (2010)Inactivation of Adenosine A(2A) Receptor Attenuates Basal and Angiotensin II-induced ROS Production by Nox2 in Endothelial Cells, In: JOURNAL OF BIOLOGICAL CHEMISTRY285(51)pp. 40104-40113 AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
D Prentice, K Boon, S Hourani (2001)Relaxation of mouse isolated aorta to adenosine and its analogues does not involve adenosine A(1), A(2) or A(3) receptors, In: EUROPEAN JOURNAL OF PHARMACOLOGY415(2-3)pp. 251-255 ELSEVIER SCIENCE BV
CD LEWIS, SMO HOURANI, CJ LONG, MG COLLIS (1994)CHARACTERIZATION OF ADENOSINE RECEPTORS IN THE RAT ISOLATED AORTA, In: GENERAL PHARMACOLOGY25(7)pp. 1381-1387 PERGAMON-ELSEVIER SCIENCE LTD
CR JOHNSON, SMO HOURANI (1994)CONTRACTILE EFFECTS OF URIDINE 5'-TRIPHOSPHATE IN THE RAT DUODENUM, In: BRITISH JOURNAL OF PHARMACOLOGY113(4)pp. 1191-1196 STOCKTON PRESS
DA HALL, SMO HOURANI (1993)EFFECTS OF ANALOGS OF ADENINE-NUCLEOTIDES ON INCREASES IN INTRACELLULAR CALCIUM MEDIATED BY P2T-PURINOCEPTORS ON HUMAN BLOOD-PLATELETS, In: BRITISH JOURNAL OF PHARMACOLOGY108(3)pp. 728-733 STOCKTON PRESS
DJ Prentice, MDW Kelly, C Ledent, SMO Hourani (2002)Relaxation of the mouse isolated aorta and carotid artery in response to adenosine analogues in genetically-modified mice lacking the adenosine A(2A) receptor, In: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY366(2)pp. 127-133 SPRINGER-VERLAG
P Zanos, P Georgiou, SR Wright, SM Hourani, I Kitchen, R Winsky-Sommerer, A Bailey (2014)The oxytocin analogue carbetocin prevents emotional impairment and stress-induced reinstatement of opioid-seeking in morphine-abstinent mice, In: Neuropsychopharmacology39(4)pp. 855-865

The main challenge in treating opioid addicts is to maintain abstinence due to the affective consequences associated with withdrawal which may trigger relapse. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin (OT) in the modulation of mood disorders as well as drug addiction. However, its involvement in the emotional consequences of drug abstinence remains unclear. We investigated the effect of 7-day opioid abstinence on the oxytocinergic system and assessed the effect of the OT analogue carbetocin (CBT) on the emotional consequences of opioid abstinence, as well as relapse. Male C57BL/6J mice were treated with a chronic escalating-dose morphine regimen (20-100 mg/kg/day, i.p.). Seven days withdrawal from this administration paradigm induced a decrease of hypothalamic OT levels and a concomitant increase of oxytocin receptor (OTR) binding in the lateral septum and amygdala. Although no physical withdrawal symptoms or alterations in the plasma corticosterone levels were observed after 7 days of abstinence, mice exhibited increased anxiety-like and depressive-like behaviors and impaired sociability. CBT (6.4 mg/kg, i.p.) attenuated the observed negative emotional consequences of opioid withdrawal. Furthermore, in the conditioned place preference paradigm with 10 mg/kg morphine conditioning, CBT (6.4 mg/kg, i.p.) was able to prevent the stress-induced reinstatement to morphine-seeking following extinction. Overall, our results suggest that alterations of the oxytocinergic system contribute to the mechanisms underlying anxiety, depression, and social deficits observed during opioid abstinence. This study also highlights the oxytocinergic system as a target for developing pharmacotherapy for the treatment of emotional impairment associated with abstinence and thereby prevention of relapse.

DA HALL, V FROST, SMO HOURANI (1994)EFFECTS OF EXTRACELLULAR DIVALENT-CATIONS ON RESPONSES OF HUMAN BLOOD-PLATELETS TO ADENOSINE 5'-DIPHOSPHATE, In: BIOCHEMICAL PHARMACOLOGY48(7)pp. 1319-1326 PERGAMON-ELSEVIER SCIENCE LTD
A Bailey, C Ledent, MDW Kelly, I Kitchen, SMO Hourani (2004)Interactions between opioid receptors and the adenosine system, In: FUNDAMENTAL & CLINICAL PHARMACOLOGY18pp. 15-15 WILEY-BLACKWELL
SMO HOURANI, CR JOHNSON, SJ BAILEY (1993)DESENSITIZATION OF THE P(2)-PURINOCEPTORS ON THE RAT COLON MUSCULARIS MUCOSAE, In: BRITISH JOURNAL OF PHARMACOLOGY110(1)pp. 501-505 STOCKTON PRESS
R Al-Hasani, JD Foster, A Metaxas, C Ledent, SM Hourani, I Kitchen, Y Chen (2011)Increased desensitization of dopamine D(2) receptor-mediated response in the ventral tegmental area in the absence of adenosine A(2A) receptors., In: Neuroscience190pp. 103-111 Elsevier

G-protein coupled receptors interact to provide additional regulatory mechanisms for neurotransmitter signaling. Adenosine A(2A) receptors are expressed at a high density in striatal neurons, where they closely interact with dopamine D(2) receptors and modulate effects of dopamine and responses to psychostimulants. A(2A) receptors are expressed at much lower densities in other forebrain neurons but play a more prominent yet opposing role to striatal receptors in response to psychostimulants in mice. It is, therefore, possible that A(2A) receptors expressed at low levels elsewhere in the brain may also regulate neurotransmitter systems and modulate neuronal functions. Dopamine D(2) receptors play an important role in autoinhibition of neuronal firing in dopamine neurons of the ventral tegmental area (VTA) and dopamine release in other brain areas. Here, we examined the effect of A(2A) receptor deletion on D(2) receptor-mediated inhibition of neuronal firing in dopamine neurons in the VTA. Spontaneous activity of dopamine neurons was recorded in midbrain slices, and concentration-dependent effects of the dopamine D(2) receptor agonist, quinpirole, was compared between wild-type and A(2A) knockout mice. The potency of quinpirole applied in single concentrations and the expression of D(2) receptors were not altered in the VTA of the knockout mice. However, quinpirole applied in stepwise escalating concentrations caused significantly reduced maximal inhibition in A(2A) knockout mice, indicating an enhanced agonist-induced desensitization of D(2) receptors in the absence of A(2A) receptors. The A(2A) receptor agonist, CGS21680, did not exert any effect on dopamine neuron firing or response to quinpirole, revealing a novel non-pharmacological interaction between adenosine A(2A) receptors and dopaminergic neurotransmission in midbrain dopamine neurons. Altered D(2) receptor desensitization may result in changes in dopamine neuron firing rate and pattern and dopamine release in other brain areas in response to persistent dopamine release and administration of psychostimulants.

SJ BAILEY, SMO HOURANI (1994)DIFFERENTIAL-EFFECTS OF SURAMIN ON P-2-PURINOCEPTORS MEDIATING CONTRACTION OF THE GUINEA-PIG VAS-DEFERENS AND URINARY-BLADDER, In: BRITISH JOURNAL OF PHARMACOLOGY112(1)pp. 219-225 STOCKTON PRESS
SMO HOURANI, DAD JONES (1994)POSTJUNCTIONAL EXCITATORY ADENOSINE A(1) RECEPTORS IN THE RAT VAS-DEFERENS, In: GENERAL PHARMACOLOGY25(3)pp. 417-420 PERGAMON-ELSEVIER SCIENCE LTD
SMO HOURANI, DA HALL (1994)RECEPTORS FOR ADP ON HUMAN BLOOD-PLATELETS, In: TRENDS IN PHARMACOLOGICAL SCIENCES15(4)pp. 103-108 ELSEVIER SCI LTD
JA Peachey, SMO Hourani, I Kitchen (1999)Ontogeny of adenosine receptors in the longitudinal muscle and muscularis mucosae of the rat distal colon, In: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY359(2)pp. 140-146 SPRINGER VERLAG