The effect of acetylcholine, oxytocin and prostaglandin F_(2α) (PGF_(2α)) on cyclic nucleotide levels in estrogen-primed rabbit whole uterus were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiestrase inhibitor, and indomethacin, a prostagandin inhibitor.
In the absence of MIX, acetylcholine increased guanosine 3´, 5´ cyclic monophosphate (cGMP), but had no effect on adenosine 3´, 5´-cyclic monophosphate (cAMP) levels. In contrast, oxytocin had no influence on cGMP, but decreased cAMP levels. PGF_(2α) increased cGMP and decreased cAMP levels.
MIX increased both cAMP and cGMP levels. Oxytocin and PGF_(2α) further increased cGMP levels, indicating activation of guanylate cyclase activity The ratio of cAMP/cGMP was decreased by uterine stinulants both in presence and absence of MIX.
Indomethacin elevated cAMP and cGMP revels. The effects of uterine stimulants in the presence of indomethacin on cyclic nucleotide levels were varied from tissue to tisse. In general, oxytocin decreased cGMP and PGF_(2α) increased cAMP/cGMP levels, but the effects were statisically nonsignicficant. The cAMP/cGMP ratio was increased by uterine stimulant in the presence of indomethacin.
In conclusion, uterine stimulants eased cAMP/cGMP ratio which indicates that the uterine stimulants have opposing effects on adenylate cyclase and guanylate cyclase activities. The endometriusm plays a role in the regulation of cyclic nucleotide levels and uterine contraction by means of PG synthesis. Indomethacin has an unknown activities besides both of PG synthetase and phosphodiesterase inhibitions.
|