Chorion-induced myometrial relaxation is mediated by large-conductance Ca2+-activated K+ channel opening in the guinea pig.
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.


METHODS
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.


CONCLUSIONS
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.
Carvajal
Jorge A
JA
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland Baltimore, School of Medicine, Baltimore, MD 21201, USA.
Thompson
Loren P
LP
Weiner
Carl P
CP
D000818:Animals; D002823:Chorion / Q000502:physiology*; D017077:Culture Media, Conditioned; D046508:Culture Techniques; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D015640:Ion Channel Gating / Q000502:physiology*; D009126:Muscle Relaxation; D009215:Myometrium / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D011247:Pregnancy; D019789:Tetraethylammonium / Q000494:pharmacology; D013873:Thionucleotides; D014590:Uterine Contraction
D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D010455:Peptides; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D013873:Thionucleotides; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; D019789:Tetraethylammonium; C064719:iberiotoxin; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP