Evidence for an inotropic positive action of cGMP during excitation-contraction coupling in frog sartorius muscle.

Within the realm of the general hypothesis concerning the role of cGMP on intracellular calcium regulation in biological systems, we have investigated the action of cyclic nucleotides during excitation-contraction coupling in frog sartorius muscle. Our data show that several guanosine nucleotides (GTP, GDP, dibutyryl-cGMP) can increase the isometric twitch tension with a maximum increase of 40% in the muscles treated with cGMP. This increase is completely independent of external Ca2+ concentration. The use of dantrolene sodium (known to inhibit calcium release from sarcoplasmic reticulum) results in a decrease in the twitch tension with a contemporary decrease in the intracellular levels of cGMP; whereas, the addition of cGMP to the muscles treated with dantrolene antagonizes, at least partially, the effect of the drug on tension development. Finally, in chemically skinned muscles, cGMP induces a reversible contracture equal to approximately one-half of that evoked by 10(-4) M Ca2+.