Human fetal membranes release a Ca++ channel inhibitor.
OBJECTIVE
Our purpose was to test the hypothesis that an inhibitor of uterine contractions released by human fetal membranes acts on the dihydropyridine site of the myometrial voltage-dependent Ca++ L channel.


METHODS
Initial experiments established the time course of release of the inhibitor from term, fetal membranes. Both a competitive binding assay and a uterine contraction bioassay were used to detect the inhibitor. After optimal time of release of inhibitor was determined, a dose-response experiment was performed with the competitive binding assay. To determine the source of the inhibitor, membranes are separated into component layers to generate inhibitor, and the competitive binding assay was used to measure the inhibitor.


RESULTS
An inhibitor released from fetal membranes competes with 3H-isradipine at the Ca++ L channel dihydropyridine binding site. There is a time-dependent release of the inhibitor from membranes, which is maximal at 20 minutes (P < or = .05, n = 4). A dose effect of the inhibitor is present because greater amounts of inhibitor produce greater competition at the dihydropyridine site (P < or = .005, n = 3). The data are consistent with 1-site binding. Inhibition is restricted to the chorion (64% specific inhibition) and decidua (52% specific inhibition) with little competition seen in amnion alone (4% specific inhibition) (P < or = .03, n = 3).


CONCLUSIONS
These studies support the hypothesis that human chorion/decidua releases an inhibitor of uterine contractions that acts specifically at the dihydropyridine site of the myometrial Ca++ L channel.
Emery
S P
SP
Department of Obstetrics and Gynecology, MetroHealth Medical Center, and Cleveland Clinic Foundation, Ohio, USA.
Idriss
E
E
Richmonds
C
C
Collins
P L
PL
D000650:Amnion / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001681:Biological Assay; D002121:Calcium Channel Blockers / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002823:Chorion / Q000378:metabolism; D003656:Decidua / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D017275:Isradipine / Q000378:metabolism; D007700:Kinetics; D011247:Pregnancy; D014316:Tritium; D014590:Uterine Contraction / Q000187:drug effects
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014316:Tritium; D017275:Isradipine