Involvement of β3-Adrenoceptor in the Relaxation Response in Guinea Pig Taenia Caecum

Abstract

ABSTRACT-13-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 p2-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 affin ity (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 /2 and (33-adrenoceptors, whereas CGP 12177-induced relaxation is mediated solely through 33-adrenoceptors.

Signal Transduction Pathway Involved in β3-Adrenoceptor-Mediated Relaxation in Guinea Pig Taenia Caecum

“…Butoxamine (10-6-10-5 M), a selective (32-adrenoceptor antagonist, caused competitive antagonism of the relaxant responses. The Schild plot of the data revealed the pA2 value of 6.46 ± 0.06, which was the same as the previously reported one (8). Butoxamine did not significantly affect the relaxant responses to CGP 12177, as previously reported (8).…”

“…We have reported that predominantly /32-and partly /33-adrenoceptors (atypical /3-adrenoceptor) are involved in the /3-adrenoceptor-mediated relaxation of the guinea pig taenia caecum and that CGP 12177 (a /31//32-adrenoceptor antagonist and a /33-adrenoceptor agonist)-induced relaxation of the guinea pig taenia caecum is solely mediated through /33-adrenoceptors (8).…”

The .BETA.2- and .BETA.3-Adrenoceptor-Mediated Relaxation Induced by Fenoterol in Guinea Pig Taenia Caecum.

“…The Schild slope of 1.06 indicates the competitive nature of the antagonism. The pA2 value for butoxamine calculated from the Schild plot (6.33) is in good agreement with the generally accepted value (6.20) (Koike et al, 1994), indicating a predominance of β2-adrenoceptors.…”

“…Previously, we have demonstrated that both the β2-and the β3-adrenoceptors are involved in the β-adrenoceptor-mediated relaxation of the guinea pig taenia caecum (Koike et al, 1994;1995a;1995b). In the present studies, fenoterol-induced relaxation of the guinea pig taenia caecum was antagonized in a concentration-dependent manner by butoxamine, a β2-selective antagonist.…”

“…We had demonstrated that the β2-and β3-adrenoceptors are involved in the β-adrenoceptormediated relaxation of the guinea pig taenia caecum (Koike et al, 1994;1995a;1995b), although the β1-adrenoceptors are not involved (Koike et al, 1994). Our previous studies also showed that the relaxant responses to isoprenaline and salbutamol, which belong to the Correspondence to: Y. Akimoto, Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan Phone: +81-47-472-1419+81-47-472- Fax: +81-47-472-1419 arylethanolamine class, are mediated by both the β2-and the β3-adrenoceptors in the guinea pig taenia caecum (Koike et al, 1997).…”