Jorge A Carvajal1, Loren P Thompson, Carl P Weiner. 1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland Baltimore, School of Medicine, Baltimore, MD 21201, USA.
Abstract
OBJECTIVE: We previously demonstrated that chorion releases a factor that inhibits both spontaneous and oxytocin-stimulated myometrial contractility. Here, we investigate the mechanism of action of this unidentified substance. STUDY DESIGN: Myometrial strips from pregnant guinea pigs were mounted in an organ bath and contractility stimulated with oxytocin. RESULTS: Guinea pig chorion produced a time-dependent decrease in oxytocin-induced myometrial contractility. The ability of the chorion to reduce contractility was unaltered by inhibiting chorionic synthesis of either nitric oxide (N [omega]-nitro-L-arginine), carbon monoxide (tin-protoporphyrin), prostaglandins (indomethacin), or the myometrial cyclic guanosine monophosphate pathway (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalime-1-one and Rp-8Br-cGMP). In contrast, iberiotoxin, an inhibitor of large conductance Ca(2+)-activated K(+) channels reduced the quiescent effect of chorion by 40%; in contrast, inhibition of adenosine triphosphate-sensitive (glibenclamide) and voltage-gated K(+) channels (4amynopyridine) had no effect. CONCLUSION: Chorion-induced relaxation of oxytocin-stimulated myometrial contraction is, in great part, the product of a paracrine substance that opens myometrial large conductance Ca(2+)-activated K(+) channels.
OBJECTIVE: We previously demonstrated that chorion releases a factor that inhibits both spontaneous and oxytocin-stimulated myometrial contractility. Here, we investigate the mechanism of action of this unidentified substance. STUDY DESIGN: Myometrial strips from pregnant guinea pigs were mounted in an organ bath and contractility stimulated with oxytocin. RESULTS:Guinea pig chorion produced a time-dependent decrease in oxytocin-induced myometrial contractility. The ability of the chorion to reduce contractility was unaltered by inhibiting chorionic synthesis of either nitric oxide (N [omega]-nitro-L-arginine), carbon monoxide (tin-protoporphyrin), prostaglandins (indomethacin), or the myometrial cyclic guanosine monophosphate pathway (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalime-1-one and Rp-8Br-cGMP). In contrast, iberiotoxin, an inhibitor of large conductance Ca(2+)-activated K(+) channels reduced the quiescent effect of chorion by 40%; in contrast, inhibition of adenosine triphosphate-sensitive (glibenclamide) and voltage-gated K(+) channels (4amynopyridine) had no effect. CONCLUSION: Chorion-induced relaxation of oxytocin-stimulated myometrial contraction is, in great part, the product of a paracrine substance that opens myometrial large conductance Ca(2+)-activated K(+) channels.
Authors: Carl P Weiner; Clifford W Mason; Yafeng Dong; Irina A Buhimschi; Peter W Swaan; Catalin S Buhimschi Journal: Am J Obstet Gynecol Date: 2010-05 Impact factor: 8.661