Inhibition of skeletal muscle sarcoplasmic reticulum Ca2+-ATPase by nitricoxide

The effects of nitric oxide on the activities of thapsigargin-sensitive sar coplasmic reticulum Ca2+-ATPase (SERCA) and Ca2+ uptake by sarcoplasmic ret iculum (SR) membranes prepared from white skeletal muscle of rabbit femoral muscle were studied. Pretreatment of the SR preparations with nitric oxide at concentrations of up to 250 mu M for 1 min decreased the SERCA activity concentration dependently, and also decreased their Ca2+ uptake. Both thes e effects of nitric oxide were reversible. Inhibitors of guanylyl cyclase a nd protein kinase G (PKG) had no significant effect on the nitric oxide-ind uced inhibitions of SERCA and Ca2+ uptake. Moreover, dithiothreitol did not reverse the inhibitory effects of nitric oxide on SERCA and Ca2+ uptake, T hese findings suggest that nitric oxide inhibits SERCA, mainly SERCA 1, of rabbit femoral skeletal muscle by an action independent of the cyclic GMP-P KG system or oxidation of thiols, and probably by a direct action on SERCA protein. (C) 1998 Federation of European Biochemical Societies.