OXYTOCIN ENHANCES THE BASAL RELEASE OF UTERINE PROSTAGLANDIN-F2-ALPHA, BUT NOT THAT OF PROSTAGLANDIN-PGE1, OR OF PROSTAGLANDIN-PGE2, AND CHANGES THE METABOLISM OF EXOGENOUS ARACHIDONATE, FAVORING THE FORMATION OF PROSTAGLANDIN-F2-ALPHA AND 5-HETE - RELATIONSHIPS WITH ITS UTEROTONIC ACTION AND MODULATION BY ESTRADIOL

We attempted to explore possible mechanism(s) subserving the influence of oxytocin on uterine motility by studying the action of the hormone on: 1) the contractile activity of isolated rat uteri in the presence or absence of indomethacin; 2) the synthesis and release of prostaglandins (PGs) into the solution incubating the uterine tissue as well as the metabolism of labelled arachidonic acid; 3) the uptake of 45Ca2+ by uterine strips. The experiments were bone with uterine preparations isolated from spayed rats treated or not with 17-beta-estradiol. The values of isometric developed tension (IDT) and of frequency of contractions (FC) induced by oxytocin in uterine strips isolated from spayed and spayed-estrogenized rats, were not modified by indomethacin at 10-6 M. On the other hand, uterine strips from untreated spayed rats, release into the incubating medium approximately equal amounts of PGE1, PGE2 and PGF2α. The in vitro presence of oxytocin (50 mU/ml) increased significantly (p 0.05) the output of PGF2α without changing the release of PGE1 or PGE2. Uteri from spayed rats injected prior to sacrifice with 17-beta-estradiol released significantly less PGE1 and PGE2 (p<0.005) than preparations from non-injected animals, whereas the output of PGF2α in the suspending solution remained unchanged. Following estrogenization the addition of oxytocin to preparations obtained from spayed-estrogenized rats also increased the output of uterine PGF2α (p<0.001) without changing that of PGs E1 or E2. Control spayed rat uteri transform labelled arachidonic acid into different cyclooxygenase metabolites such as 6-keto-PGF1α, TXB2, PGF2α and PGE2 as well as into lipoxygenase metabolites, such us 5-HETE. The in vitro addition of oxytocin (50 mU/ml) increased the formation of PGF2α (p<0.05) and 5-HETE (p<0.05) without changing the generation of other metabolites. Estrogenization of the spayed rats diminished significantly the uterine formation of 6-keto-PGF1α (p<0.001) and PGE2 (p<0.05) but increased that of 5-HETE (p<0.05). Regarding the formation of 5-HETE and PGF2α the action of oxytocin on the metabolism of arachidonic acid by the uterine tissue isolated from spayed-estrogenized rats, was the same as in the corresponding controls. On the other hand the addition of oxytocin (50 mU/ml) increased significantly (p<0.01) 45Ca2+ uptake by uterine strips from spayed rats. Estrogenization of spayed rats, also augmented 45Ca2+ uptake by rat uterine strips. However the addition of oxytocin to uterine strips obtained from spayed-estrogenized animals failed to alter the effects of estrogenization, its action was similar to that evoked in uteri from untreated spayed rats. The present findings suggest that oxytocin has an uterotonic Ca2+ mediated influence (not modified by indomethacin) and a PGF2α and 5-HETE releasing action which apparently is not linked to the oxytocin inotropic influence. © 1990.