Cyclic nucleotides and myometrial contractility

Cyclic nucleotides determine a spatiotemporally regulated system that modulates uterine myometrial contractility and parturition timing. Adenylate and guanylate cyclases synthesize cAMP and cGMP upon beta-adrenergic, natriuretic peptide, and nitric oxide stimulation. Before parturition, cAMP suppresses contraction-associated protein synthesis via PKA, and cGMP activates hyperpolarizing K+ current via PKG. At term, cAMP stimulates contraction-associated protein expression via EPAC just as decreasing PKG attenuates cGMP tocolysis. The cAMP-specific phosphodiesterase 4 (PDE4) facilitates myometrial contraction by degrading cyclic nucleotides. The precise roles of cGMP on myometrial activation and the effect of other PDEs in parturition are not yet clear. Strategies to reduce preterm birth could benefit from a better understanding of the myometrial cyclic nucleotide system.