Cyclic AMP-independent relaxation mediated by beta3-adrenoceptors on guinea pig gastrointestine.
In this study, we investigated the signal transduction pathway involved in beta(3)-adrenoceptor-mediated relaxations of guinea pig gastric fundus and duodenum. In the presence of beta1- and beta2-adrenoceptor blockade, the potency (pD2 value) of catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline) and beta(3)-adrenoceptor agonists ((R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid sodium (BRL37344) and (+/-)-[4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride ((+/-)-CGP12177A)) to induce relaxation was not affected by the adenylate cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ-22,536, 100 microM). Catecholamines induced an elevation of cyclic AMP and SQ-22,536 significantly abolished the responses of gastric fundus. However, cyclic AMP levels were unaltered by the beta3-adrenoceptor agonists in gastric fundus and by the five agonists in duodenum. Furthermore, the relaxant responses to catecholamines and to beta3-adrenoceptor agonists were unaffected by the cyclic AMP-dependent protein kinase inhibitor, N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H-89, 10 microM) in gastric fundus. These results suggest that beta3-adrenoceptor-induced relaxation is mediated through both cyclic AMP-dependent and cyclic AMP-independent pathways in gastric fundus and through a cyclic AMP-independent pathway in duodenum.
Horinouchi
Takahiro
T
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Funabashi, Chiba, Japan.
Koike
Katsuo
K
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004064:Digestive System / Q000187:drug effects; D004068:Digestive System Physiological Phenomena; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000502:physiology*
D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; D002078:Butoxamine; C017759:9-(tetrahydro-2-furyl)-adenine; C057368:BRL 37344; D011433:Propranolol; D000242:Cyclic AMP; D000225:Adenine; C033394:CGP 12177