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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

beta(3)-Adrenoceptor agonist stimulation of the Na(+),K(+)-pump in rat skeletal muscle is mediated by beta(2)- rather than beta(3)-adrenoceptors.

Background and purpose:In cardiac muscle, BRL 37344, a selective beta(3)-adrenoceptor agonist, activates the Na(+),K(+)-pump via NO signalling. This study investigated whether BRL 37344 also activates the Na(+),K(+)-pump via beta(3)-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 (86)Rb(+) 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 (86)Rb(+) uptake by up to 112%. BRL 37344-induced reductions in intracellular Na(+) were blocked by the beta(1)/beta(2)-adrenoceptor antagonist, nadolol (10(-7) M), and the beta(2)-adrenoceptor antagonist, ICI 118,551 (10(-7)-10(-5) M), but not by beta(3)- or beta(1)-adrenoceptor antagonists, SR 59230A (10(-7) M) and CGP 20712A (10(-7)-10(-5) M), respectively. Another beta(3)-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 beta(3)-adrenoceptor agonist BRL 37344 stimulated the Na(+),K(+)-pump via beta(2)-adrenoceptors. A more selective beta(3)-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; published online 3 October 2006.[1]


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