β₃‐Adrenoceptor agonist stimulation of the Na⁺,K⁺‐pump in rat skeletal muscle is mediated by β₂‐ rather than β₃‐adrenoceptors

Background and purpose:In cardiac muscle, BRL 37344, a selective β3‐adrenoceptor agonist, activates the Na+,K+‐pump via NO signalling. This study investigated whether BRL 37344 also activates the Na+,K+‐pump via β3‐adrenoceptors in skeletal muscle.Experimental approach:Isolated rat soleus muscles were incubated between 1 and 60 min in buffer. Intracellular Na+,K+ content and Na+,K+‐pump activity were measured using flame photometry and ouabain‐suppressible 86Rb+ uptake, respectively. Additional muscles were mounted on force transducers and stimulated (60 Hz for 2 s) every 10 min.Key results:BRL 37344 (10‐8‐10‐5 M) induced a concentration‐ and time‐dependent reduction in intracellular Na+, and increased ouabain‐suppressible 86Rb+ uptake by up to 112%. BRL 37344‐induced reductions in intracellular Na+ were blocked by the β1/β2‐adrenoceptor antagonist, nadolol (10‐7 M), and the β2‐adrenoceptor antagonist, ICI 118,551 (10‐7‐10‐5 M), but not by β3‐ or β1‐adrenoceptor antagonists, SR 59230A (10‐7 M) and CGP 20712A (10‐7‐10‐5 M), respectively. Another β3‐adrenoceptor agonist, CL 316,243, did not alter intracellular Na+. BRL 37344‐induced reductions in intracellular Na+ were not blocked by L‐NAME, an NOS inhibitor, or ODQ, a guanylyl cyclase inhibitor. The NO donors, SNP and SNAP, did not alter intracellular Na+. BRL 37344 rapidly recovered force in muscles depressed by high [K+]o, an effect that was blocked by nadolol, but not L‐NAME.Conclusions and implications:In rat soleus muscle, the β3‐adrenoceptor agonist BRL 37344 stimulated the Na+,K+‐pump via β2‐adrenoceptors. A more selective β3‐adrenoceptor agonist did not affect Na+, K+ homeostasis in skeletal muscle. NO did not seem to mediate Na+,K+‐pump stimulation in skeletal muscle.British Journal of Pharmacology (2006) 149, 635–646. doi:10.1038/sj.bjp.0706896