Cyclic AMP accumulation in rat soleus muscle: stimulation by beta2- but not beta3-adrenoceptors

The beta-adrenoceptor subtypes involved in cyclic AMP accumulation in rat soleus muscle were studied using beta1- beta2- and beta3-adrenoceptor agonists and antagonists. Responses to (-)-isoprenaline were antagonised by (-)-propranolol (p KB = 8.32 at 0.1 microM) and by erythro-DL-1(7-methylindian-4-yloxy)-3-isopropylaminobuta n-2-ol (+/-)-ICI 118551) (pKB = 9.38 at 10 nM and 9.65 at 100 nM) but not by 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H-imidazole -2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulfonate ((+/-)-CGP 20712A at 10 nM or 100 nM). The beta3-adrenoceptor agonist sodium-4-[-2[-2-hydroxy-2-(-3-chlorophenyl)ethylamino]propyl]phenoxya cetate (BRL 37344 at 10 pM or 10 microM) caused no significant change in basal cyclic AMP levels and had no effect on the level of cyclic AMP accumulation stimulated by (-)-isoprenaline, zinterol or forskolin. (-)-Isoprenaline pretreatment (400 microg kg(-1) h(-1), 14 days) abolished responses to (-)-isoprenaline (10 microM) and zinterol (1 microM) while BRL 37344 had no effect in either isoprenaline or vehicle-treated groups. These results show that beta3-adrenoceptor agonists do not stimulate cyclic AMP accumulation in rat soleus muscle and that (-)-isoprenaline induced increases in cyclic AMP levels are mediated predominantly by beta2-adrenoceptors. This suggests that the previously reported increase in glucose uptake by beta3-adrenoceptor agonists in skeletal muscle does not involve direct stimulation of adenylate cyclase.