Wells L, Opacka-Juffry J, Fisher D, Ledent C, Hourani S, Kitchen I (2011) In vivo dopaminergic and behavioural responses to acute cocaine are altered in adenosine A(2A) receptor knockout mice., Synapse 66 pp. 382-390
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
Boarder MR, Hourani SMO (1998) The regulation of vascular function by P2 receptors: multiple sites and multiple receptors, TRENDS IN PHARMACOLOGICAL SCIENCES 19 (3) pp. 99-107 ELSEVIER SCI LTD
Metaxas A, Al-Hasani R, Farshim P, Tubby K, Berwick A, Ledent C, Hourani S, Kitchen I, Bailey A (2013) Genetic deletion of the adenosine A2A receptor prevents nicotine-induced upregulation of ±7, but not ±4²2* nicotinic acetylcholine receptor binding in the brain., Neuropharmacology 71 pp. 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]±-bungarotoxin binding to ±4²2* and ±7 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 ±4²2* and ±7 nAChR binding sites were increased compared with saline treated controls. The genetic ablation of adenosine A2ARs prevented nicotine-induced upregulation of ±7 nAChRs, without affecting ±4²2* 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 ±7 nAChR upregulation, and identify A2ARs as novel pharmacological targets for modulating the long-term effects of nicotine on ±7 receptors.
Prentice DJ, Kelly MDW, Ledent C, Hourani SMO (2001) Effect of A(2A) adenosine receptor knockout on relaxant effects of adenosine and analogues in mouse isolated aorta., BRITISH JOURNAL OF PHARMACOLOGY 134 NATURE PUBLISHING GROUP
HOURANI SMO, NICHOLLS J, LEE BSS, HALFHIDE EJ, KITCHEN I (1993) CHARACTERIZATION AND ONTOGENY OF P-1-PURINOCEPTORS ON RAT VAS-DEFERENS, BRITISH JOURNAL OF PHARMACOLOGY 108 (3) pp. 754-758 STOCKTON PRESS
Wright SR, Zanos P, Georgiou P, Yoo JH, Ledent C, Hourani SM, Kitchen I, Winsky-Sommerer R, Bailey A (2015) A critical role of striatal A2A R-mGlu5 R interactions in modulating the psychomotor and drug-seeking effects of methamphetamine., Addict Biol 21 (4) pp. 811-825
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.
Zanos P, Georgiou P, Gonzalez LR, Hourani S, Chen Y, Kitchen I, Kieffer BL, Winsky-Sommerer R, Bailey A (2016) Emotional Impairment and Persistent Upregulation of mGlu5 Receptor following Morphine Abstinence: Implications of an mGlu5-MOPr Interaction., The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) 19 (7)
A difficult problem in treating opioid addicts is the maintenance of a drug-free state because of the negative emotional symptoms associated with withdrawal, which may trigger relapse. Several lines of evidence suggest a role for the metabotropic glutamate receptor 5 in opioid addiction; however, its involvement during opioid withdrawal is not clear.Mice were treated with a 7-day escalating-dose morphine administration paradigm. Following withdrawal, the development of affective behaviors was assessed using the 3-chambered box, open-field, elevated plus-maze and forced-swim tests. Metabotropic glutamate receptor 5 autoradiographic binding was performed in mouse brains undergoing chronic morphine treatment and 7 days withdrawal. Moreover, since there is evidence showing direct effects of opioid drugs on the metabotropic glutamate receptor 5 system, the presence of an metabotropic glutamate receptor 5/¼-opioid receptor interaction was assessed by performing metabotropic glutamate receptor 5 autoradiographic binding in brains of mice lacking the ¼-opioid receptor gene.Withdrawal from chronic morphine administration induced anxiety-like, depressive-like, and impaired sociability behaviors concomitant with a marked upregulation of metabotropic glutamate receptor 5 binding. Administration of the metabotropic glutamate receptor 5 antagonist, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine, reversed morphine abstinence-induced depressive-like behaviors. A brain region-specific increase in metabotropic glutamate receptor 5 binding was observed in the nucleus accumbens shell, thalamus, hypothalamus, and amygdala of ¼-opioid receptor knockout mice compared with controls.These results suggest an association between metabotropic glutamate receptor 5 alterations and the emergence of opioid withdrawal-related affective behaviors. This study supports metabotropic glutamate receptor 5 system as a target for the development of pharmacotherapies for the treatment of opioid addiction. Moreover, our data show direct effects of ¼-opioid receptor system manipulation on metabotropic glutamate receptor 5 binding in the brain.
Prentice DJ, Hourani SMO (1997) Adenosine analogues relax guinea-pig taenia caeci via an adenosine A(2B) receptor and a xanthine-resistant site, EUROPEAN JOURNAL OF PHARMACOLOGY 323 (1) pp. 103-106 ELSEVIER SCIENCE BV
Peachey JA, Hourani SMO, Kitchen I (1999) Ontogeny of adenosine receptors in the longitudinal muscle and muscularis mucosae of the rat distal colon, NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 359 (2) pp. 140-146 SPRINGER VERLAG
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
BAILEY SJ, HICKMAN D, HOURANI SMO (1992) CHARACTERIZATION OF THE P(1)-PURINOCEPTORS MEDIATING CONTRACTION OF THE RAT COLON MUSCULARIS MUCOSAE, BRITISH JOURNAL OF PHARMACOLOGY 105 (2) pp. 400-404 STOCKTON PRESS
PRENTICE DJ, HOURANI SMO (1995) NECA AND R-PIA ACTIVATE DISTINCT SITES TO CAUSE RELAXATION OF THE ISOLATED RAT AORTA, BRITISH JOURNAL OF PHARMACOLOGY 115 pp. P64-P64 STOCKTON PRESS
HOURANI SMO, CHOWN JA (1989) THE EFFECTS OF SOME POSSIBLE INHIBITORS OF ECTONUCLEOTIDASES ON THE BREAKDOWN AND PHARMACOLOGICAL EFFECTS OF ATP IN THE GUINEA-PIG URINARY-BLADDER, GENERAL PHARMACOLOGY 20 (4) pp. 413-416 PERGAMON-ELSEVIER SCIENCE LTD
Nicholls J, Brownhill VR, Hourani SMO (1996) Characterization of P-1-purinoceptors on rat isolated duodenum longitudinal muscle and muscularis mucosae, BRITISH JOURNAL OF PHARMACOLOGY 117 (1) pp. 170-174 STOCKTON PRESS
Georgiou P, Zanos P, Ehteramyan M, Hourani S, Kitchen I, Maldonado R, Bailey A (2014) Differential regulation of mGlu5 R and OPr by priming- and cue-induced reinstatement of cocaine-seeking behaviour in mice., Addict Biol 20 (5) pp. 902-912
The key problem for the treatment of drug addiction is relapse to drug use after abstinence that can be triggered by drug-associated cues, re-exposure to the drug itself and stress. Understanding the neurobiological mechanisms underlying relapse is essential in order to develop effective pharmacotherapies for its prevention. Given the evidence implicating the metabotropic glutamate receptor 5 (mGlu5 R), ¼-opioid receptor (MOPr), º-opioid receptor (OPr) and oxytocin receptor (OTR) systems in cocaine addiction and relapse, our aim was to assess the modulation of these receptors using a mouse model of cue- and priming-induced reinstatement of cocaine seeking. Male mice were trained to self-administer cocaine (1 mg/kg/infusion, i.v.) and were randomized into different groups: (1) cocaine self-administration; (2) cocaine extinction; (3) cocaine-primed (10 mg/kg i.p.); or (4) cue-induced reinstatement of cocaine seeking. Mice undergoing the same protocols but receiving saline instead of cocaine were used as controls. Quantitative autoradiography of mGlu5 R, MOPr, KOPr and OTR showed a persistent cocaine-induced upregulation of the mGlu5 R and OTR in the lateral septum and central amygdala, respectively. Moreover, a downregulation of mGlu5 R and MOPr was observed in the basolateral amygdala and striatum, respectively. Further, we showed that priming- but not cue-induced reinstatement upregulates mGlu5 R and MOPr binding in the nucleus accumbens core and basolateral amygdala, respectively, while cue- but not priming-induced reinstatement downregulates MOPr binding in caudate putamen and nucleus accumbens core. This is the first study to provide direct evidence of reinstatement-induced receptor alterations that are likely to contribute to the neurobiological mechanisms underpinning relapse to cocaine seeking.
Bailey A, Ledent C, Kelly MDW, Kitchen I, Hourani SMO (2004) Interactions between opioid receptors and the adenosine system, FUNDAMENTAL & CLINICAL PHARMACOLOGY 18 pp. 15-15 WILEY-BLACKWELL
HOURANI SMO, CUSACK NJ (1991) PHARMACOLOGICAL RECEPTORS ON BLOOD-PLATELETS, PHARMACOLOGICAL REVIEWS 43 (3) pp. 243-298 WILLIAMS & WILKINS
HALL DA, FROST V, HOURANI SMO (1994) EFFECTS OF EXTRACELLULAR DIVALENT-CATIONS ON RESPONSES OF HUMAN BLOOD-PLATELETS TO ADENOSINE 5'-DIPHOSPHATE, BIOCHEMICAL PHARMACOLOGY 48 (7) pp. 1319-1326 PERGAMON-ELSEVIER SCIENCE LTD
Brownhill VR, Hourani SMO, Kitchen I (1996) Differential ontogeny of adenosine receptors in the longitudinal muscle and muscularis mucosae of the rat isolated duodenum, EUROPEAN JOURNAL OF PHARMACOLOGY 317 (2-3) pp. 321-328 ELSEVIER SCIENCE BV
CUSACK NJ, HOURANI SMO (1991) DESIGN, SYNTHESES AND PHARMACOLOGY OF ATP ANALOGS SELECTIVE FOR SUBTYPES OF P2-PURINOCEPTORS, NUCLEOSIDES & NUCLEOTIDES 10 (5) pp. 1019-1028 MARCEL DEKKER INC
Bailey A, Weber D, Zimmer A, Zimmer AM, Hourani SMO, Kitchen I (2004) Quantitative autoradiography of adenosine receptors and NBTI-sensitive adenosine transporters in the brains of mice deficient in the preproenkephalin gene, BRAIN RESEARCH 1025 (1-2) pp. 1-9 ELSEVIER SCIENCE BV
Brownhill VR, Hourani SMO, Kitchen I (1996) Differential distribution of adenosine A(2) receptors in the epididymal and prostatic portions of the rat vas deferens, EUROPEAN JOURNAL OF PHARMACOLOGY 303 (1-2) pp. 87-90 ELSEVIER SCIENCE BV
HOURANI SMO, WELFORD LA, LOIZOU GD, CUSAK NJ (1988) ADENOSINE 5'-(2-FLUORODIPHOSPHATE) IS A SELECTIVE AGONIST AT P2-PURINOCEPTORS MEDIATING RELAXATION OF SMOOTH-MUSCLE, EUROPEAN JOURNAL OF PHARMACOLOGY 147 (1) pp. 131-136 ELSEVIER SCIENCE BV
Prentice DJ, Kelly MDW, Ledent C, Hourani SMO (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, NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 366 (2) pp. 127-133 SPRINGER-VERLAG
NICHOLLS J, HOURANI SMO, KITCHEN I (1992) CHARACTERIZATION OF P1-PURINOCEPTORS ON RAT DUODENUM AND URINARY-BLADDER, BRITISH JOURNAL OF PHARMACOLOGY 105 (3) pp. 639-642 STOCKTON PRESS
LEWIS CD, HOURANI SMO, LONG CJ, COLLIS MG (1994) CHARACTERIZATION OF ADENOSINE RECEPTORS IN THE RAT ISOLATED AORTA, GENERAL PHARMACOLOGY 25 (7) pp. 1381-1387 PERGAMON-ELSEVIER SCIENCE LTD
PEACHEY JA, BROWNHILL VR, HOURANI SMO, KITCHEN I (1995) THE ONTOGENY OF ADENOSINE RECEPTOR SUBTYPES IN THE RAT VAS-DEFERENS, BRITISH JOURNAL OF PHARMACOLOGY 115 pp. P143-P143 STOCKTON PRESS
HOURANI SMO, HALL DA (1994) RECEPTORS FOR ADP ON HUMAN BLOOD-PLATELETS, TRENDS IN PHARMACOLOGICAL SCIENCES 15 (4) pp. 103-108 ELSEVIER SCI LTD
Prentice DJ, Hourani SMO (1997) Information in agonist curve shape for receptor classification, RECEPTOR CLASSIFICATION 812 pp. 234-235 NEW YORK ACAD SCIENCES
Georgiou P, Zanos P, Garcia-Carmona J-A, Hourani S, Kitchen I, Kieffer BL, Laorden M-L, Bailey A (2015) The oxytocin analogue carbetocin prevents priming-induced reinstatement of morphine-seeking: Involvement of dopaminergic, noradrenergic and MOPr systems, EUROPEAN NEUROPSYCHOPHARMACOLOGY 25 (12) pp. 2459-2464 ELSEVIER SCIENCE BV
HALL DA, HOURANI SMO (1994) EFFECTS OF SURAMIN ON INCREASES IN CYTOSOLIC CALCIUM AND ON INHIBITION OF ADENYLATE-CYCLASE INDUCED BY ADENOSINE 5'-DIPHOSPHATE IN HUMAN PLATELETS, BIOCHEMICAL PHARMACOLOGY 47 (6) pp. 1013-1018 PERGAMON-ELSEVIER SCIENCE LTD
HOURANI SMO, BAILEY SJ, NICHOLLS J, KITCHEN I (1991) DIRECT EFFECTS OF ADENYLYL 5'-(BETA,GAMMA-METHYLENE)DIPHOSPHONATE, A STABLE ATP ANALOG, ON RELAXANT P1-PURINOCEPTORS IN SMOOTH-MUSCLE, BRITISH JOURNAL OF PHARMACOLOGY 104 (3) pp. 685-690 STOCKTON PRESS
WELFORD LA, CUSACK NJ, HOURANI SMO (1986) ATP ANALOGS AND THE GUINEA-PIG TAENIA-COLI - A COMPARISON OF THE STRUCTURE-ACTIVITY-RELATIONSHIPS OF ECTONUCLEOTIDASES WITH THOSE OF THE P-2-PURINOCEPTOR, EUROPEAN JOURNAL OF PHARMACOLOGY 129 (3) pp. 217-224 ELSEVIER SCIENCE BV
Hourani SMO, Boon K, Fooks HM, Prentice DJ (2001) Role of cyclic nucleotides in vasodilations of the rat thoracic aorta induced by adenosine analogues, BRITISH JOURNAL OF PHARMACOLOGY 133 (6) pp. 833-840 NATURE PUBLISHING GROUP
Park HS, Hourani SMO (1999) Differential effects of adenine nucleotide analogues on shape change and aggregation induced by adenosine 5 '-diphospbate (ADP) in human platelets, BRITISH JOURNAL OF PHARMACOLOGY 127 (6) pp. 1359-1366 STOCKTON PRESS
WELFORD LA, CUSACK NJ, HOURANI SMO (1987) THE STRUCTURE-ACTIVITY-RELATIONSHIPS OF ECTONUCLEOTIDASES AND OF EXCITATORY P2-PURINOCEPTORS - EVIDENCE THAT DEPHOSPHORYLATION OF ATP ANALOGS REDUCES PHARMACOLOGICAL POTENCY, EUROPEAN JOURNAL OF PHARMACOLOGY 141 (1) pp. 123-130 ELSEVIER SCIENCE BV
Hourani SMO, Bailey SJ, Johnson CR, Tennant JP (1998) Effects of adenosine 5 '-triphosphate, uridine 5 '-triphosphate, adenosine 5 '-tetraphosphate and diadenosine polyphosphates in guinea-pig taenia caeci and rat colon muscularis mucosae, NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 358 (4) pp. 464-473 SPRINGER VERLAG
Bailey A, Mathes H, Kieffer B, Slowe S, Hourani SMO, Kitchen I (2002) Quantitative autoradiography of adenosine receptors and NBTI-sensitive adenosine transporters in the brains and spinal cords of mice deficient in the mu-opioid receptor gene, BRAIN RESEARCH 943 (1) PII S0006-8993(02)02536-2 pp. 68-79 ELSEVIER SCIENCE BV
Lamb DJ, Tickner ML, Dreux AC, El-Sankary W, Hourani SMO, Eales-Reynolds LJ, Ferns GAA (2004) Impairment of vascular function following BCG immunisation is associated with immune responses to HSP-60 in the cholesterol-fed rabbit, ATHEROSCLEROSIS 172 (1) pp. 13-20 ELSEVIER SCI IRELAND LTD
Johnson CR, Charlton SJ, Hourani SMO (1996) Responses of the longitudinal muscle and the muscularis mucosae of the rat duodenum to adenine and uracil nucleotides, BRITISH JOURNAL OF PHARMACOLOGY 117 (5) pp. 823-830 STOCKTON PRESS
Hussey MJ, Clarke GD, Ledent C, Hourani SMO, Kitchen I (2007) Reduced response to the formalin test and lowered spinal NMDA glutamate receptor binding in adenosine A(2A) receptor knockout mice, PAIN 129 (3) pp. 287-294 ELSEVIER SCIENCE BV
HOURANI SMO, LOIZOU GD, CUSACK NJ (1986) PHARMACOLOGICAL EFFECTS OF L-AMP-PCP ON ATP RECEPTORS IN SMOOTH-MUSCLE, EUROPEAN JOURNAL OF PHARMACOLOGY 131 (1) pp. 99-103 ELSEVIER SCIENCE BV
PEACHEY JA, HOURANI SMO, KITCHEN I (1994) THE BINDING OF 1,3-[H-3]-DIPROPYL-8-CYCLOPENTYLXANTHINE TO ADENOSINE A(1) RECEPTORS IN RAT SMOOTH-MUSCLE PREPARATIONS, BRITISH JOURNAL OF PHARMACOLOGY 113 (4) pp. 1249-1256 STOCKTON PRESS
HOURANI SMO, JONES DAD (1994) POSTJUNCTIONAL EXCITATORY ADENOSINE A(1) RECEPTORS IN THE RAT VAS-DEFERENS, GENERAL PHARMACOLOGY 25 (3) pp. 417-420 PERGAMON-ELSEVIER SCIENCE LTD
BAILEY SJ, HOURANI SMO (1995) EFFECTS OF SURAMIN ON CONTRACTIONS OF THE GUINEA-PIG VAS-DEFERENS INDUCED BY ANALOGS OF ADENOSINE 5'-TRIPHOSPHATE, BRITISH JOURNAL OF PHARMACOLOGY 114 (6) pp. 1125-1132 STOCKTON PRESS
HOURANI SMO, JOHNSON CR, BAILEY SJ (1993) DESENSITIZATION OF THE P(2)-PURINOCEPTORS ON THE RAT COLON MUSCULARIS MUCOSAE, BRITISH JOURNAL OF PHARMACOLOGY 110 (1) pp. 501-505 STOCKTON PRESS
Ferre S, Diamond I, Goldberg SR, Yao L, Hourani SMO, Huang ZL, Urade Y, Kitchen I (2007) Adenosine A(2A) receptors in ventral striatum, hypothalamus and nociceptive circuitry - Implications for drug addiction, sleep and pain, PROGRESS IN NEUROBIOLOGY 83 (5) pp. 332-347 PERGAMON-ELSEVIER SCIENCE LTD
Lewis CD, Hourani SMO (1997) Involvement of functional antagonism in the effects of adenosine antagonists and L-NAME in the rat isolated heart, GENERAL PHARMACOLOGY 29 (3) pp. 421-427 PERGAMON-ELSEVIER SCIENCE LTD
Hourani SMO (1999) Postnatal development of purinoceptors in rat visceral smooth muscle preparations, GENERAL PHARMACOLOGY 32 (1) pp. 3-7 PERGAMON-ELSEVIER SCIENCE LTD
BAILEY SJ, HOURANI SMO (1994) DIFFERENTIAL-EFFECTS OF SURAMIN ON P-2-PURINOCEPTORS MEDIATING CONTRACTION OF THE GUINEA-PIG VAS-DEFERENS AND URINARY-BLADDER, BRITISH JOURNAL OF PHARMACOLOGY 112 (1) pp. 219-225 STOCKTON PRESS
Hourani SMO, Welford LA, Cusack NJ (1996) Effects of 2-methylthioadenosine 5'-beta,gamma-methylenetriphosphonate and 2-ethyithioadenosine 5'-monophosphate on human platelet activation induced by adenosine 5'-diphosphate, DRUG DEVELOPMENT RESEARCH 38 (1) pp. 12-23 WILEY-LISS
Prentice DJ, Hourani SMO (2000) Characterisation of adenosine receptors mediating relaxation in hamster isolated aorta, NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 362 (4-5) pp. 427-434 SPRINGER-VERLAG
PEACHEY JA, HOURANI SMO, KITCHEN I (1994) ADENOSINE-A(1) BINDING-SITES IN RAT SMOOTH-MUSCLE PREPARATIONS, BRITISH JOURNAL OF PHARMACOLOGY 111 pp. P323-P323 STOCKTON PRESS
Tennant JP, Callaghan F, Turner C, Hourani SMO (1999) Effects of allopurinol, erythro-9-(2-hydroxy-3-nonyl)adenine and S-(4-nitrobenzyl)-6-thioinosine on the degradation of adenosine 5 '-triphosphate in the rat colon muscularis mucosae, JOURNAL OF AUTONOMIC PHARMACOLOGY 19 (4) pp. 229-232 BLACKWELL SCIENCE LTD
Godfrey L, Hourani SMO, Kitchen I (2003) Quantitative autoradiography of [H-3]paracetamol binding in the mouse brain, BRITISH JOURNAL OF PHARMACOLOGY 140 NATURE PUBLISHING GROUP
Nicholls J, Hourani SMO (1997) Characterization of adenosine receptors on rat ileum, ileal longitudinal muscle and muscularis mucosae, EUROPEAN JOURNAL OF PHARMACOLOGY 338 (2) pp. 143-150 ELSEVIER SCIENCE BV
Prentice DJ, Hourani SMO (1996) Activation of multiple sites by adenosine analogues in the rat isolated aorta, BRITISH JOURNAL OF PHARMACOLOGY 118 (6) pp. 1509-1517 STOCKTON PRESS
HOURANI SMO, BAILEY SJ, NICHOLLS J, KITCHEN I (1991) AMPPCP ACTS VIA P1-RECEPTORS AND NOT P2-RECEPTORS IN SOME ISOLATED SMOOTH-MUSCLE PREPARATIONS, NUCLEOSIDES & NUCLEOTIDES 10 (5) pp. 1203-1205 MARCEL DEKKER INC
Prentice DJ, Payne SL, Hourani SMO (1997) Activation of two sites by adenosine receptor agonists to cause relaxation in rat isolated mesenteric artery, BRITISH JOURNAL OF PHARMACOLOGY 122 (7) pp. 1509-1515 STOCKTON PRESS
Bailey A, Hawkins RM, Hourani SMO, Kitchen I (2003) Quantitative autoradiography of adenosine receptors in brains of chronic naltrexone-treated mice, BRITISH JOURNAL OF PHARMACOLOGY 139 (6) pp. 1187-1195 NATURE PUBLISHING GROUP
Bailey A, Davis L, Lesscher HMB, Kelly MDW, Ledent C, Hourani SMO, Kitchen I (2004) Enhanced morphine withdrawal and mu-opioid receptor G-protein coupling in A(2A) adenosine receptor knockout ti ice, JOURNAL OF NEUROCHEMISTRY 88 (4) pp. 827-834 BLACKWELL PUBLISHING LTD
Tickner ML, Lamb DJ, Dreux AC, El-Sankary W, Hourani S, Eales-Reynolds LJ, Ferns GAA (2003) BCG immunisation impairs vascular relaxation and enhances atherosclerosis in the chronically hypercholesterolaemic rabbit, BRITISH JOURNAL OF PHARMACOLOGY 140 NATURE PUBLISHING GROUP
BAILEY SJ, HOURANI SMO (1990) A STUDY OF THE PURINOCEPTORS MEDIATING CONTRACTION IN THE RAT COLON, BRITISH JOURNAL OF PHARMACOLOGY 100 (4) pp. 753-756 STOCKTON PRESS
Belchamber K, Hall DA, Hourani SM (2014) Smoking enhances the proinflammatory effects of nucleotides on cytokine release from human lung., PLoS One 9 (6)
Nucleotides have effects on immune cells which are complex but generally proinflammatory, and have been suggested to play a role in smoking-related lung diseases. However, there have been no studies directly measuring functional responses to nucleotides in human lungs taken from smokers. We used fragments of post mortem human lung from smokers and non-smokers, incubated them with a range of nucleotides (4-1000 µM) in the presence of lipopolysaccharide (LPS; 10 µg/ml) for 24 hours and measured cytokines (IL-1², IFN³, IL-17, TNF±, IL-6, IL-8, IL-2 and IL-10) in the supernatants using multiplex immunoassays. Although the basal cytokine levels in the smokers were generally higher in the smokers than the non-smokers, there were no significant differences in either the basal release or the LPS-stimulated release of any of the cytokines when lungs from smokers and non-smokers were compared. There were no significant effects of ATP, ADP, AMP, UTP, ±,²-methylene-ATP, P1, P4-diATP, 2-methylthio-ATP or Bz-ATP on the release of cytokines from the lungs. However, the stable ATP analogue ATP³S increased the release of IL-1² and IFN³, and the effect was greatly increased in lungs from smokers. In non-smokers but not in smokers ATP³S increased the release of IL-17. Overall these results clearly demonstrate for the first time that in normal human lung a stable ATP analogue can enhance LPS-induced pro-inflammatory cytokine release, and that these effects are greatly altered by a prior history of smoking. This provides strong support for the suggestion that nucleotides are involved in the pathogenesis of smoking-related diseases.
Tennant JP, Samuel EJ, Hourani SMO (1997) Ectonucleotidase activity in the prostatic and epididymal portions of the guinea-pig vasdeferens, BRITISH JOURNAL OF PHARMACOLOGY 122 pp. P146-P146 STOCKTON PRESS
Kelly MDW, Ledent C, Kitchen I, Hourani SMO (2003) Characterization of [H-3]-ZM 241385 binding in wildtype and A(2A) knockout mouse brain, BRITISH JOURNAL OF PHARMACOLOGY 140 NATURE PUBLISHING GROUP
Georgiou P, Zanos P, Garcia-Carmona JA, Hourani S, Kitchen I, Laorden ML, Bailey A (2016) Methamphetamine abstinence induces changes in ¼-opioid receptor, oxytocin and CRF systems: Association with an anxiogenic phenotype., Neuropharmacology 105 pp. 520-532
The major challenge in treating methamphetamine addicts is the maintenance of a drug free-state since they experience negative emotional symptoms during abstinence, which may trigger relapse. The neuronal mechanisms underlying long-term withdrawal and relapse are currently not well-understood. There is evidence suggesting a role of the oxytocin (OTR), ¼-opioid receptor (MOPr), dopamine D2 receptor (D2R), corticotropin-releasing factor (CRF) systems and the hypothalamic-pituitary-adrenal (HPA)-axis in the different stages of methamphetamine addiction. In this study, we aimed to characterize the behavioral effects of methamphetamine withdrawal in mice and to assess the modulation of the OTR, MOPr, D2R, CRF and HPA-axis following chronic methamphetamine administration and withdrawal. Ten-day methamphetamine administration (2 mg/kg) increased OTR binding in the amygdala, whilst 7 days of withdrawal induced an upregulation of this receptor in the lateral septum. Chronic methamphetamine treatment increased plasma OT levels that returned to control levels following withdrawal. In addition, methamphetamine administration and withdrawal increased striatal MOPr binding, as well as c-Fos(+)/CRF(+) neuronal expression in the amygdala, whereas an increase in plasma corticosterone levels was observed following METH administration, but not withdrawal. No differences were observed in the D2R binding following METH administration and withdrawal. The alterations in the OTR, MOPr and CRF systems occurred concomitantly with the emergence of anxiety-related symptoms and the development of psychomotor sensitization during withdrawal. Collectively, our findings indicate that chronic methamphetamine use and abstinence can induce brain-region specific neuroadaptations of the OTR, MOPr and CRF systems, which may, at least, partly explain the withdrawal-related anxiogenic effects.
Park HS, Tennant JP, Waktolla GF, Sarkardei S, Kass GEN, Hourani SMO (1998) Effects of adenosine 3 '-phosphate 5 '-phosphosulfate on P2 receptors in platelets and smooth muscle preparations, DRUG DEVELOPMENT RESEARCH 45 (2) pp. 67-73 WILEY-LISS
Hourani SMO, Hall DA (1996) P2T purinoceptors: ADP receptors on platelets, P2 PURINOCEPTORS: LOCALIZATION, FUNCTION AND TRANSDUCTION MECHANISMS 198 pp. 53-70 JOHN WILEY & SONS LTD
Hourani SMO (1996) Purinoceptors and platelet aggregation, JOURNAL OF AUTONOMIC PHARMACOLOGY 16 (6) pp. 349-352 BLACKWELL SCIENCE LTD
Hourani SMO, Smith NC, Nettell JJ, Hall JM (1997) Relaxation of the ovine isolated iris sphincter by adenosine receptor agonists: Lack of effect of adenosine A(1) and A(2) receptor antagonists, EUROPEAN JOURNAL OF PHARMACOLOGY 334 (1) pp. 95-98 ELSEVIER SCIENCE BV
Nicholls J, Skene DJ, Hourani SMO (1997) Use of a newly developed technique to isolate rat pinealocytes and study the effects of adenosine agonists on melatonin production, JOURNAL OF PINEAL RESEARCH 23 (3) pp. 164-168 WILEY-BLACKWELL
Ribe D, Sawbridge D, Thakur S, Hussey M, Ledent C, Kitchen I, Hourani S, Li J-M (2008) Adenosine A(2A) receptor signaling regulation of cardiac NADPH oxidase activity, FREE RADICAL BIOLOGY AND MEDICINE 44 (7) pp. 1433-1442 ELSEVIER SCIENCE INC
Zanos P, Georgiou P, Wright SR, Hourani SM, Kitchen I, Winsky-Sommerer R, Bailey A (2013) The Oxytocin Analogue Carbetocin Prevents Emotional Impairment and Stress-Induced Reinstatement of Opioid-Seeking in Morphine-Abstinent Mice., Neuropsychopharmacology
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.Neuropsychopharmacology advance online publication, 4 December 2013; doi:10.1038/npp.2013.285.
Tennant JP, Pearson A, Hourani SMO (1999) Effects of noradrenaline, the calcium ionophore A23 187, forskolin, sodium nitroprusside and glibenclamide on the degradation of extracellular adenosine 5 '-triphosphate by the rat isolated vas deferens, JOURNAL OF AUTONOMIC PHARMACOLOGY 19 (3) pp. 167-171 BLACKWELL SCIENCE LTD
Geeson J, Larsson K, Hourani SM, Toms NJ (2002) Sodium nitroprusside-induced rat fundus relaxation is ryanodine-sensitive and involves L-type Ca2+ channel and small conductance Ca(2+)-sensitive K+ channel components., Auton Autacoid Pharmacol 22 (5-6) pp. 297-301
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.
Oxidative stress attributable to the activation of a Nox2-containing NADPH oxidase is involved in dietary obesity-associated cardiovascular diseases. However, the mechanism of Nox2 activation in dietary obesity remains unclear. In this project age-matched apolipoprotein E knockout (ApoEKO) and Nox2/ApoE double knockout (D-KO) mice were used to investigate high-fat diet (HFD)-induced obesity-related metabolic disorders, Nox2 activation, endothelial and adipose tissue dysfunction.
Compared to NCD, HFD ApoEKO mice developed insulin resistance, increased systemic oxidative stress and vascular dysfunction which was accompanied by increased Nox2 expression, activated mitogen-activated protein kinase (MAPK) and attenuated Akt/endothelial nitric oxide synthesis (eNOS) pathways. Akt was decreased, vascular cell adhesion molecule-1 was increased and macrophages were recruited indicating endothelial cell activation and inflammation, attenuating the phosphatidylinositol-3-kinase/Akt/eNOS branch in favour of the MAPK. In vitro experiments showed that in response to high glucose/insulin challenge, ApoEKO aortas increased significantly the levels of Nox2 expression, activation of stress signalling pathways and the cells were senescent. Finally, the relationship of Nox2-derived reactive oxygen species due to obesity and adipose tissue dysfunction was examined for the first time in ApoEKO mice. It was found that adipose tissue in obesity is infiltrated by macrophages and intercellular adhesion molecule-1 is increased. Insulin receptor is decreased whereas ERK phosphorylation is increased and eNOS phosphorylation is decreased suggesting impaired insulin signalling. Uncoupled protein-1 levels also decreased. Nox2/ApoE D-KO mice did not exhibit any of the delirious effects of HFD/ insulin resistance and were protected from adipose tissue inflammation.
In conclusion, this project demonstrated a crucial role for metabolic disorders in systemic Nox2 activation, inflammation, endothelial dysfunction and insulin receptor function in HFD ApoEKO mice. Also, it provides novel insights into mechanisms underlying adipose tissue dysfunction. Therefore, Nox2 targeting may represent an effective therapy to preserve endothelial and adipose tissue function and improve global metabolism in dietary obesity.