Signal transduction pathway involved in beta 3-adrenoceptor-mediated relaxation in guinea pig taenia caecum.

Experiments were carried out to examine the components of the intracellular second messenger system that is involved in beta 3-adrenoceptor (atypical beta-adrenoceptors)-mediated relaxation in the guinea pig taenia caecum. Propranolol and butoxamine caused competitive antagonism of the relaxant response to isoprenaline. However, propranolol or butoxamine did not significantly affect the relaxant responses to CGP 12177 (4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H- benzimidazol-2-one), a beta 3-adrenoceptor agonist. The concentration-response curves of the isoprenaline-induced increase in adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels were shifted to the right in a parallel manner by propranolol and butoxamine. However, propranolol or butoxamine did not significantly affect the concentration-response curve for the CGP 12177-induced increase in cyclic AMP levels. MDL 12330 (cis-N-(2-phenylcyclopentyl)-azacyclotridec-1-en-2-amine) inhibited the isoprenaline- or CGP 12177-induced increase in cyclic AMP levels. These results suggest that the production of cyclic AMP contributes to the beta 3-adrenoceptor (or atypical beta-adrenoceptor)-mediated relaxation of the guinea pig taenia caecum.