The β-adrenoceptor subtypes involved in cyclic AMP accumulation in rat soleus muscle were studied using β1- β2- and β3-adrenoceptor agonists and antagonists. Responses to (-)-isoprenaline were antagonised by (-)- propranolol (pK(B) = 8.32 at 0.1 μM) and by erythro-DL-1(7-methylindian-4- yloxy)-3-isopropylaminobutan-2-ol ((±)-ICI 118551) (pK(B) = 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 β3- adrenoceptor agonist sodium-4-[-2[-2-hydroxy-2-(-3- chlorophenyl)ethylamino]propyl]phenoxyacetate (BRL 37344 at 10 pM or 10 μM) 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 μg kg-1 h-1, 14 days) abolished responses to (-)-isoprenaline (10 μM) and zinterol (1 μM) while BRL 37344 had no effect in either isoprenaline or vehicle-treated groups. These results show that β3-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 β2- adrenoceptors. This suggests that the previously reported increase in glucose uptake by β3-adrenoceptor agonists in skeletal muscle does not involve direct stimulation of adenylate cyclase.
- BRL 37344
- Soleus muscle