Involvement of beta 3-adrenoceptor in the relaxation response in guinea pig taenia caecum.
beta-Adrenoceptors in the guinea pig taenia caecum were investigated by measuring relaxation responses to agonists and by a radioligand binding assay using [3H]CGP 12177. The rightward shift of the isoprenaline concentration-response curve was observed by butoxamine, a beta 2-selective antagonist, and the pA2 value for butoxamine was 6.46. In control preparations, catecholamines caused relaxation with the following rank order of potency: isoprenaline > adrenaline > noradrenaline. However, in the presence of 10(-6) M phentolamine, 3 x 10(-4) M atenolol and 10(-4) M butoxamine, the rank order of potency of the agonists was: isoprenaline > noradrenaline > adrenaline. CGP 12177 caused graded relaxation of the guinea pig taenia caecum, and this response was not influenced by 10(-6) M phentolamine, 3 x 10(-4) M atenolol, 10(-4) M butoxamine or 10(-6) M propranolol. The Scatchard plot of the specific [3H]CGP 12177 binding to microsomal fractions from the guinea pig taenia caecum showed two affinity sites of the receptor: high affinity (KD = 0.64 nM) and low affinity (KD = 142.21 nM) sites. The pKD value of the high affinity site of [3H]CGP 12177 was in agreement with its pA2 value, and that of the low affinity site was in agreement with its pD2 value. These results suggest that isoprenaline-, noradrenaline- and adrenaline-induced relaxations of the guinea pig taenia caecum predominantly involve beta 2- and beta 3-adrenoceptors, whereas CGP 12177-induced relaxation is mediated solely through beta 3-adrenoceptors.
Koike
K
K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Takayanagi
I
I
Muramatsu
M
M
Ohki
S
S
Horinouchi
T
T
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002078:Butoxamine / Q000378:metabolism / Q000494:pharmacology; D002432:Cecum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010646:Phentolamine / Q000378:metabolism / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D002078:Butoxamine; D001262:Atenolol; D007545:Isoproterenol; C033394:CGP 12177; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine