Partial agonistic activity of labetalol, the arylethanolamine, on beta 3-adrenoceptors in the guinea-pig gastric fundus.
1. The agonistic and antagonistic effects of labetalol, the alpha1- and beta-adrenoceptor antagonist, were studied on beta3-adrenoceptors in the guinea-pig gastric fundus. 2. Labetalol caused a concentration-dependent relaxation with a pD2 value of 5.58 +/- 0.09 and an intrinsic activity of 0.64 +/- 0.06, which was not affected by pretreatment with both the selective beta1-adrenoceptor antagonist, (+/-)-atenolol (100 microM), and the selective beta2-adrenoceptor antagonist, (+/-)-butoxamine (100 microM). 3. However, the non-selective beta1-, beta2- and beta3-adrenoceptor antagonist, (+/-)-bupranolol (3-30 microM), shifted the concentration-response curve of labetalol to the right (pA2 value=5.97 +/- 0.08). 4. In the presence of (+/-)-atenolol (100 microM) and (+/-)-butoxamine (100 microM), relaxations to catecholamines [(-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline], to the selective beta3-adrenoceptor agonist, BRL37344, and to the non-conventional partial beta3-adrenoceptor agonist, (+/-)-CGP12177A, were weakly antagonized by labetalol (10 microM). 5. These results indicate that labetalol, the arylethanolamine, acts as a partial agonist on beta3-adrenoceptors in the guinea-pig gastric fundus.
Horinouchi
T
T
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Asai
S
S
Fukushima
M
M
Koike
K
K
D058667:Adrenergic beta-3 Receptor Agonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019856:Ethanolamine / Q000737:chemistry / Q000494:pharmacology*; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007741:Labetalol / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology
D058667:Adrenergic beta-3 Receptor Agonists; D022702:Receptors, Adrenergic, beta-3; D019856:Ethanolamine; D007741:Labetalol