Effect of bupranolol for BRL37344 and noradrenaline-induced relaxations mediating atypical beta/beta3-adrenoceptor in rat oesophageal muscularis mucosae.
We previously suggested that the existence of atypical beta/beta3-adrenoceptor with pA2-values for bupranolol, a non-selective beta-adrenoceptor antagonist, against BRL37344 and noradrenaline were 5.79 and 5.53 in guinea pig taenia caecum, respectively. We furthermore determined the affinity of bupranolol to subclassify atypical beta/beta3-adrenoceptor in rat oesophageal muscularis mucosae, because it is rich in atypical beta/beta3-adrenoceptor. BRL37344 and noradrenaline produced a concentration-dependent relaxation of rat oesophageal muscularis mucosae. The responses to BRL37344 and noradrenaline were resistant to 3x10(-6) M propranolol, 10(-4) M atenolol, and 10(-4) M butoxamine. However, bupranolol antagonized the responses to BRL37344 and noradrenaline in a concentration-dependent manner. Schild plot analyses of bupranolol against BRL37344 and noradrenaline gave pA2-values of 7.06 and 6.96, respectively. These results suggest that bupranolol can distinguish the difference in affinity between atypical beta/beta3-adrenoceptors in rat oesophageal muscularis mucosae and guinea pig taenia caecum. The difference in behavior of bupranolol confirms the existence of some atypical beta/beta3-adrenoceptors subtypes.
Horinouchi
T
T
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Koshikawa
H
H
Koike
K
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002046:Bupranolol / Q000494:pharmacology*; D004947:Esophagus / Q000737:chemistry / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology; D008297:Male; D009092:Mucous Membrane / Q000737:chemistry / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D022702:Receptors, Adrenergic, beta-3
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C057368:BRL 37344; D002046:Bupranolol; D009638:Norepinephrine