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.

DOI: 10.1038/sj.bjp.0706896

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