Involvement of calcitonin gene-related peptide in the modulation of human myometrial contractility during pregnancy

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and relaxes smooth muscle of a variety of tissues, but the effects of CGRP on human myo metrial contractions and the changes in CGRP receptors (CGRP-Rs) in human m yometrium have not been described. We report that CGRP induced dose-depende nt relaxation in spontaneously contracting myometrium from pregnant women. This relaxation effect is diminished in myometrium obtained from patients d uring labor and in the nonpregnant state. CGRP-induced relaxations are inhi bited by a CGRP-R antagonist (CGRP(8-37)), a soluble guanylate cyclase inhi bitor (LY83583), and a nitric oxide synthase inhibitor (L-NAME). Both Weste rn blotting and mRNA analysis showed that CGRP-Rs are present in human myom etrium, and that the expression of these receptors is increased during preg nancy and decreased during term labor. Immunofluorescent staining revealed that CGRP-Rs are abundant in the myometrial cells of pregnant women who are not in labor, and are minimal in uterine specimens from women in labor and in the nonpregnant state. We conclude that increased CGRP-Rs in myometrium , and resulting enhanced myometrial sensitivity to CGRP, may play a role in maintaining human myometrium in a quiescent state during pregnancy, and th at a decline in the CGRP-Rs at term could contribute to the initiation of l abor.