Effects of cGMP on [Ca2+]i, myosin light chain phosphorylation, and contraction in human myometrium

Abstract

Adenosine 3',5'-cyclic monophosphate (cAMP) is believed to be an important mediator of myometrial relaxation, and there is evidence to suggest that guanosine 3',5'-cyclic monophosphate (cGMP) is a mediator of smooth muscle relaxation in vascular and probably nonvascular tissues. To investigate the biochemical mechanisms involved in regulation of human myometrial contractility, we studied the effects of analogues of cAMP and cGMP, as well as activators of adenylate and guanylate cyclases, on uterine smooth muscle contractile activity. We found that myometrial smooth muscle cells in culture respond to analogues of cGMP and cAMP, as well as activators of guanylate cyclase, with a significant decrease in the resting and endothelin-induced increase in [Ca2+]i. Treatment of human uterine smooth muscle strips with sodium nitroprusside or isoproterenol results in diminished force and frequency of contraction as well as a decrease in the rate and extent of myosin light chain phosphorylation in spontaneous contractions of human myometrium. cGMP did not effect relaxation of endothelin-stimulated contractions of human myometrium, but the relaxation effects of cGMP were dramatic in precontracted bovine tracheal and human fetal aortic smooth muscles. Whereas cGMP and cAMP act to promote a decrease in the force and frequency of spontaneous contractions in human myometrium, this tissue is not as responsive to the actions of cyclic nucleotides as are other types of smooth muscle.