8-bromoguanosino-3--5--cyclic-monophosphorothioate and iberiotoxin

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.. Myometrial strips from pregnant guinea pigs were mounted in an organ bath and contractility stimulated with oxytocin.. 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.. 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.

Topics: Animals; Chorion; Culture Media, Conditioned; Culture Techniques; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Enzyme Inhibitors; Female; Guinea Pigs; Ion Channel Gating; Muscle Relaxation; Myometrium; Peptides; Potassium Channel Blockers; Potassium Channels, Calcium-Activated; Pregnancy; Tetraethylammonium; Thionucleotides; Uterine Contraction