Abnormality of calcium channel inhibitor released from fetal membranes in preterm labor

OBJECTIVE: This study was undertaken to test the hypothesis that an inhibit or of uterine contractions acting at the level of the dihydropyridine recep tor of the uterine L-type uterine calcium channel is released in greater am ounts from fetal membranes before term than at term, STUDY DESIGN: Endogenous calcium channel inhibitor activity was generated w ith standardized 25-cm(2) surface area fetal membrane samples from the foll owing 4 categories of women: preterm in labor, preterm not in labor, term i n labor, and term not in labor. The amount of inhibitor in each membrane ca tegory was quantified by means of a competitive binding assay. Inhibition o f uterine contractions induced by Bay K 8644 (an L-type calcium channel ago nist) was used as another test of endogenous calcium channel inhibitor acti vity released from fetal membranes of all 4 groups of patients. RESULTS: Endogenous calcium channel inhibitor activity was most variable bu t present in the greatest amount in fetal membranes of women who were prete rm not in labor followed by those in women at term not in labor and at term in labor. Fetal membranes from women in preterm labor had the least amount of measured endogenous calcium channel inhibitor activity. Consistent with the competitive binding assay, endogenous calcium channel inhibitor activi ty from fetal membranes from women who were preterm not in labor, at term n ot in labor, and at term in labor inhibited Bay K 8644-induced uterine cont ractions. Fetal membranes from women in preterm labor did not inhibit Bay K 8644-induced contractions. Endogenous calcium channel inhibitor activity w as present in the chorion, the decidua, and the placenta, with little activ ity in the amnion, CONCLUSION: The down-regulation of endogenous calcium channel inhibitor act ivity with advancing gestation is consistent with a potential role for this inhibitor in maintaining uterine quiescence and in regulating the transiti on into labor. One possible cause of idiopathic preterm labor may be an abn ormally low amount of endogenous calcium channel inhibitor activity in feta l membranes.