title: Angiotensin II-induced activation of central AT1 receptors exerts endocannabinoid-mediated gastroprotective effect in rats.
abstract: The aim of the present study was to analyze whether angiotensin II via the endocannabinoid system can induce gastric mucosal protection, since transactivation of cannabinoid CB1 receptors by angiotensin AT1 receptor in CHO cells was described. Experimental ulcer was induced by acidified ethanol given orally in male Wistar rats, CB1(+/+) wild type and CB1(-/-) knockout mice. The compounds were administered intracerebroventricularly. It was found, that 1. Angiotensin II inhibited the ethanol-induced gastric lesions (11.9-191pmol); the effect of angiotensin II (191pmol) was inhibited by the CB1 receptor inverse agonist AM 251 (1.8nmol) and the inhibitor of diacylglycerol lipase (DAGL), tetrahydrolipstatin (0.2nmol). 2. Angiotensin II exerted gastroprotection in wild type, but not in CB1(-/-) mice. 3. The gastroprotective effect of angiotensin II (191pmol) was reduced by atropine (1mg/kg i.v.) and bilateral cervical vagotomy. In conclusion, stimulation of central angiotensin AT1 receptors via activation of cannabinoid CB1 receptors induces gastroprotection in a DAGL-dependent and vagus-mediated mechanism.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., 1089 Budapest, Hungary. Electronic address: gyirkla@net.sote.hu.
authors.forename: Klára
authors.initials: K
authors.lastname: Gyires
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., 1089 Budapest, Hungary.
authors.forename: András Z
authors.initials: AZ
authors.lastname: Rónai
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., 1089 Budapest, Hungary.
authors.forename: Zoltán S
authors.initials: ZS
authors.lastname: Zádori
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., 1089 Budapest, Hungary.
authors.forename: Viktória E
authors.initials: VE
authors.lastname: Tóth
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Debrecen, Nagyerdei krt. 98., 4032 Debrecen, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Németh
authors.affiliation: Department of Physiology, Faculty of Medicine, Semmelweis University, Tűzoltó u. 37-47., 1094 Budapest, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Szekeres
authors.affiliation: Department of Physiology, Faculty of Medicine, Semmelweis University, Tűzoltó u. 37-47., 1094 Budapest, Hungary; Laboratory of Molecular Physiology, Semmelweis University and Hungarian Academy of Sciences, Tűzoltó u. 37-47., 1094 Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Hunyady
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016466:CHO Cells; D003412:Cricetulus; D000431:Ethanol; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation; D007276:Injections, Intraventricular; D007783:Lactones / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000077403:Orlistat; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014628:Vagotomy; D014630:Vagus Nerve
chemical_list: D007783:Lactones; D010880:Piperidines; D011720:Pyrazoles; D044140:Receptor, Angiotensin, Type 1; D043884:Receptor, Cannabinoid, CB1; D000804:Angiotensin II; C103505:AM 251; D000431:Ethanol; D001285:Atropine; D000077403:Orlistat; D008071:Lipoprotein Lipase
keywords: 2-AG; 2-arachidonoylglycerol; AT(1) receptor; Ang II; Angiotensin II; CB(1) KO mice; CGRP; CHO; Chinese hamster ovary; DAG; DAG lipase; Endocannabinoids; Gastroprotection; Rat; THL; angiotensin AT(1) receptor; angiotensin II; calcitonin gene-related peptide; diacylglycerol; diacylglycerol lipase; tetrahydrolipstatin