Functional properties of atypical beta-adrenoceptors on the guinea pig duodenum.
In this study, we attempted to further characterize atypical beta-adrenoceptors on the guinea pig duodenum. (-)-Enantiomers of isoprenaline and noradrenaline were more potent than its (+)-enantiomers. The isomeric activity ratios ((+)/(-)) were less than those obtained in the guinea pig atria and trachea. The concentration-response curves to catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), to the selective beta(3)-adrenoceptor agonist, BRL37344 ((R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid sodium), and to the non-conventional partial beta(3)-adrenoceptor agonist, (+/-)-CGP12177A ((+/-)-[4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride), were resistant to blockade by (+/-)-pindobind, the beta-adrenoceptor alkylating agent. (-)-Noradrenaline and (-)-adrenaline were more potent than dopamine and (-)-phenylephrine, respectively. Selective beta(2)-adrenoceptor agonists possess agonistic activities at atypical beta-adrenoceptors. (+/-)-Propranolol and (+/-)-bupranolol had no agonistic effect, whereas (+/-)-alprenolol, (+/-)-pindolol, (+/-)-nadolol, (+/-)-CGP12177A and (+/-)-carteolol exhibited agonistic activities at atypical beta-adrenoceptors. These results suggest that pharmacological properties of atypical beta-adrenoceptors differ from those of conventional beta(1)- and beta(2)-adrenoceptors on the guinea pig.
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Chiba 274-8510, Funabashi, Japan
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Horinouchi
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Koike
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000737:chemistry / Q000494:pharmacology; D000526:Alprenolol / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002046:Bupranolol / Q000737:chemistry / Q000494:pharmacology; D002354:Carteolol / Q000737:chemistry / Q000494:pharmacology; D002976:Clenbuterol / Q000737:chemistry / Q000494:pharmacology; D004280:Dobutamine / Q000737:chemistry / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000737:chemistry / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005280:Fenoterol / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009248:Nadolol / Q000737:chemistry / Q000494:pharmacology; D009638:Norepinephrine / Q000737:chemistry / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010869:Pindolol / Q000737:chemistry / Q000494:pharmacology; D011412:Propanolamines / Q000737:chemistry / Q000494:pharmacology; D011433:Propranolol / Q000737:chemistry / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013237:Stereoisomerism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D005280:Fenoterol; D004280:Dobutamine; D009248:Nadolol; C057368:BRL 37344; D002046:Bupranolol; D000526:Alprenolol; D002354:Carteolol; D011433:Propranolol; D010869:Pindolol; D007545:Isoproterenol; D000420:Albuterol; C033394:CGP 12177; D004298:Dopamine; D009638:Norepinephrine; D002976:Clenbuterol; D004837:Epinephrine