CYCLIC-AMP ACCUMULATION IN RAT SOLEUS MUSCLE - STIMULATION BY BETA(2)-ADRENOCEPTOR BUT NOT BETA(3)-ADRENOCEPTOR

The beta-adrenoceptor subtypes involved in cyclic AMP accumulation in rat soleus muscle were studied using beta(1)- beta(2)- and beta(3)-adr enoceptor agonists and antagonists. Responses to (-)-isoprenaline were antagonised by (-)-propranolol (pK(B) = 8.32 at 0.1 mu M) and by 7-me thylindian-4-yloxy)-3-isopropylaminobutan-2-ol ((+/-)-ICI 118551) (pK( B) = 9.38 at 10 nM and 9.65 at 100 nM) but not by azole-2-yl)-phenoxy) propyl)amino)ethoxy)-benzamide monomethane sulfonate ((+/-)-CGP 20712A at 10 nM or 100 nM). The beta(3)-adrenoceptor agonist -(-3-chlorophen yl)ethylamino]propyl]phenoxyacetate (BRL 373411 at 10 pM or 10 mu M) c aused no significant change in basal cyclic AMP levels and had no effe ct on the level of cyclic AMP accumulation stimulated by (-)-isoprenal ine, zinterol or forskolin. (-)-Isoprenaline pretreatment (400 mu g kg (-1) h(-1), 14 days) abolished responses to (-)-isoprenaline (10 mu M) and zinterol(1 mu M) while BRL 37344 had no effect in either isoprena line or vehicle-treated groups. These results show that beta(3)-adreno ceptor agonists do not stimulate cyclic AMP accumulation in rat soleus muscle and that (-)-isoprenaline induced increases in cyclic AMP leve ls are mediated predominantly by beta(2)-adrenoceptors. This suggests that the previously reported increase in glucose uptake by beta(3)-adr enoceptor agonists in skeletal muscle does not involve direct stimulat ion of adenylate cyclase. (C) 1998 Elsevier Science B.V.