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In this study we explored the possible underlying mechanism(s) of the differential transport of unfertilized and fertilized ova in cycling and pregnant rats. The number of ova recovered from rat oviducts and uterus was not significantly different in estrus, metestrus and diestrus but dropped sharply at proestrus. When estrus rats were injected with indomethacin (10(-6)), a well known inhibitor of cyclooxygenase, delivered into both ovarian bursae, and sacrificed next day at metestrus, the number of ova in the oviduct was significantly smaller (p less than 0.025) than in controls at metestrus. On the other hand, when diestrus rats were injected with PGE1 (10(-6)) delivered into both ovarian bursae, and sacrificed next day at proestrus, no ova were found in the oviducts, and only a few of them were in the uterus. When fertilized ova were recovered from oviducts and uteri at day 4 of pregnancy (corresponding to proestrus of cycling rats) an average of 4 embryos were still found in the oviducts, proving a differential ovum transport between cycling and pregnant rats. In order to establish if there exists any ova or embryo releasing factor responsible for this difference, the prostaglandins released to the incubation medium by ovum or 3-day embryo were measured. Unfertilized ova produced significantly more PGE1 (p less than 0.05) than PGE2 or PGF2 alpha. The same pattern of PG production was observed with incubated embryos, but in this case the amount of PGE1 released was significantly higher (p less than 0.01) that the PGE1 released by unfertilized ova.(ABSTRACT TRUNCATED AT 250 WORDS)

The possible existence of a selective and independent mechanism subserving the formation of prostaglandin E1 (PGE1) and of prostaglandin E2 (PGE2) has been reported in previous studies from our group. In the present experiments we have demonstrated that neutral lipid lipases play an important role yielding dihomo-gamma-linolenic acid for the formation of PGE1. Indeed, exogenous triglyceride lipase added to the incubation bathing solution at a concentration of 150 U/ml increased several fold the production of PGE1 by isolated uterine strips obtained from spayed rats. Nevertheless the presence of the enzyme did not modify significantly the synthesis and release of bisenoic PGs (PGE2 and PGF2 alpha). When triarachidonin was added, as an artificial substrate into the incubating medium in order to detect the presence of endogenous triacylglycerol lipase, we observed a significant increment in the generation of PGE2 (p less than 0.005) and of PGF2 alpha (p less than 0.001) without evident changes in the basal release of PGE1. On the other hand, the addition of phospholipase A2 (PLA2) at 0.2 U/ml, increased significantly the production of PGE2 (p less than 0.001) but failed to alter the concentration of PGE1 in the incubating solution. Surprisingly, PLA2 did not enhance the synthesis of PGF2 alpha in the present experiments, a situation for which we do not have a clear explanation. Exogenous bradykinin (10(-6) M), a well known stimulant of PLA2 activity in several tissues, also increased significantly (p less than 0.001) the production of PGE2 without altering that of PGE1.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study was performed in order to explore the influence of ova present within rat oviducts on: a) tubal spontaneous motility and b) oviduct prostaglandin production. It was found that the isometric developed tension (IDT) of tubes isolated from proestrous rats (preovulatory oviducts) was significantly higher (P less than 0.01) than the IDT of tubes from rats at estrus and at metestrus (postovulatory oviducts). After flushing the oviducts with KRB solution (i.e., after removing existing ova) the IDT of the oviducts obtained from estrous rats increased significantly (P less than 0.01), whereas the IDT of tubes isolated from proestrous rats (i.e., preparations without ova) was not modified. On the other hand, isolated tubes containing their corresponding ova released into the suspending solution significantly more PGE1 than PGE2 or PGF2 alpha (P less than 0.005). It was particularly interesting to find that after flushing the oviducts, tissue production of PGE1, PGE2 and PGF2 alpha was similar. Finally, when dose response curves for PGE1 and for PGE2 on the spontaneous contractions of oviducts isolated from rats at proestrus, estrus and metestrus were constructed, both PGs evoked an inhibitory inotropic action. The ED50 for PGE1 in tubes from estrous rats was significantly smaller (P less than 0.01) than that for metestrous animals but significantly greater (P less than 0.01) than that observed in oviducts from proestrous rats. The ED50 for PGE2 did not change in the different tested periods of the sex cycle. Results reported herein suggest the possibility that the ova present within rat oviducts, may influence their own transport along the tubes by modifying the amount of prostaglandins produced by the oviducts or via their own prostaglandin synthesis.

The present study reports findings on: a) the action of histamine (H) on the spontaneous motility of the uterus isolated from rats during four different stages of the sex cycle; b) the relevance of endogenous and exogenous prostaglandins (PGs) for the inotropic effect of H and c) the relationships between these factors and the generation and release of PGs in rat uterine horns obtained during proestrus, estrus, metestrus and diestrus. Cumulative dose-response curves for H, in strips isolated from proestrous rats, showed that the agonist inhibited, at all the concentrations tested, spontaneous myometrial contractions, evoking a maximum effect (100% inhibition) at 10(-5)M. Incubation with acetylsalicylic acid (ASA; 10(-4)M) did not modify the dose-response curve for H. In strips from estrous rats, the maximum effect of H was obtained at 10(-3)M and, after incubating with ASA, the control dose-response curve for H was shifted to the left. A subthreshold dose of PGE2 (10(-9)M), reversed completely the action of ASA on H uterine responses, whereas PGF2 alpha was not effective. Dose-response curves for H, in uterine strips isolated from metestrous rats, showed the maximum effect (85% of inhibition) at 10(-3)M. Incubation with ASA, shifted the curve to the left and, the maximum effect increased up to 100% inhibition. A subthreshold dose (10(-9)M) of PGE2 or of PGF2 alpha shifted to the right the dose-response curve for the amine. In uterine strips isolated from diestrous rats the maximum inotropic action of H evoked only 75% of contractile inhibition and, in the presence the ASA, this influence reached 100%; the dose-response for the agonist being shifted to the left. Both PGE2 or PGF2 alpha, added in the presence of ASA, abolished the displacement evoked by ASA on the control dose-response curve for H. A significant correlation between the tissue output of "PGE-like material" into the bathing solution and the ED50 for the contractile influence of H, was also detected. On the contrary the release of "PGF2 alpha -like material" did not correlate with the ED50 for H. The foregoing results suggest that some endogenous uterine prostaglandins of the 2 series, modulate the depressive inotropic action of H in isolated uterine strips, depending on the ovarian hormonal status of the animals.

The purpose of the present study was to explore whether, the stimulating contractile action of angiotensin II (AII) or of angiotensin I (AI), in uterine strips isolated from rats, either spayed or spayed and injected with 17-beta estradiol, was somehow linked to tissue generated prostaglandins (PGs). Indomethacin (10(-6)M), shifted to the left the dose-response curve for AII in preparations from ovariectomized animals; augmenting both, the efficacy and the potency of the agonist. Dose-response curves for AII were also explored in the presence of subthreshold concentrations of several exogenous PGs. PGE2 (10(-9) M) completely abolished the influence of indomethacin on the curve for AII; PGD2 (10(-9) M) did not evoke effects and PGF2 alpha (10(-9) M) only altered the threshold dose, the rest of the curve remaining similar to that obtained with indomethacin alone. The cumulative dose-response curve for AI, in strips isolated from ovariectomized rats, was comparable to that for AII and, the presence of indomethacin, only reduced the concentration for the threshold action of AI, in comparison to controls. Captopril (100 ng/ml), shifted to the right the dose-response curve for AI and indomethacin failed to alter the effects of AI in the presence of captopril. In strips isolated from ovariectomized rats, injected with 17-beta estradiol, the low concentration points of the dose-response curve for AII were shifted to the left of those for the agonist in control preparations from spayed rats not treated with estradiol. Furthermore, indomethacin failed to alter the responses to AII in strips from spayed animals injected with 17-beta estradiol. The foregoing results document that an inhibitor of tissue PGs synthesis, namely indomethacin, is able to modify the dose-response curve for AII, rather than that for AI, in the uterus from ovariectomized rats, but not in preparations from spayed animals treated with estradiol. This, as well as the effect of a subthreshold dose of PGs, suggest that a minimum of PGE2 is required for the contractile influence of AII and not for that of AI. Moreover, the absence of estrogen dominance appears, as well, as a crucial factor for the action of AII.

3H-dihydroalprenolol (DHA) -- receptor binding was studied in membrane preparations from metestrous uterine tissue, both in presence and absence of exogenous prostaglandin (PG) F2 alpha at 10(-9) M. In addition, the uptake of 3H-noradrenaline (NA) by uterine segments from estrous and metestrous rats and the influences of PGF2 alpha (10(-9) M), cocaine (10(-5) M) corticosterone (5.10(-5) M), normetanephrine (10(-6) M) or acetylsalicylic acid (ASA: 10(-4) M), were explored. The Scatchard analysis of experimental data with 3H-DHA with or without added PGF2 alpha indicates the existence of a single class of high affinity receptors and no differences were found, in presence of PGF2 alpha, regarding the control dissociation constant or the control maximal sites of specific binding. On the other hand, the uptake of 3H-NA by uterine segments at metestrus was significantly greater than at estrus. In metestrous uteri PGF2 alpha (10(-9) M) reduced significantly NA uptake. ASA enhanced NA uptake by uteri from estrous rats, an influence prevented by PGF2 mu. In uterine segments isolated at estrus, cocaine, corticosterone and normetanephrine failed to alter 3H-NA uptake, whereas in preparations isolated at metestrus, corticosterone and normetanephrine reduced the uptake, but cocaine did not evoke any influence. Results are discussed in terms of previous findings documenting an amplification of the negative inotropic influence of NA mediated by the activation of beta-adrenoceptors, both in estrous or in metestrous preparations incubated with PGF2 alpha. Such previous findings cannot be explained by changes in the number of NA receptors or by a greater affinity of tissue receptors for the agonist, but rather by differences in NA uptake controlling its effective concentration at the biophase, near receptor sites. Interrelationships along sex hormones (estradiol), prostaglandins (PGF2 alpha) and catecholamines (NA) in uteri, are also discussed.

Cumulative dose-response curves for histamine induced responses in mesometrial (ME) and antimesometrial (AME) regions of uterine horns isolated from rats at 7th, 16th and 22nd days of pregnancy, were constructed. Histamine inhibited, in dose-related fashion, the isometric developed tension in ME and AME strips obtained at the 7th day of pregnancy, an action antagonized by cimetidine (10(-4)-10(-5) M). On the contrary, at the 16th and 22nd days, histamine (10(-5)-10(-3) M), stimulated spontaneous contractions in the ME region but had no effect in the AME segment. Although histamine and SKF-71481-A2,aH1-receptor agonist, both at 10(-4) M, enhanced similarly ME inotropism at the 16th and at 22nd days of pregnancy, the positive contractile action of histamine was greater at the 16th than at the 22nd day. Moreover, cumulative dose-response curves for histamine and SKF-71481-A2 in the ME region of uteri isolated at the 16th day of gestation, showed that both agonists have approximately the same inotropic potency and efficacy. On the other hand, pyrilamine (at 10(-4) M, but not at 10(-5) M aH1-receptor antagonist, shifted to the right the dose-response curve for histamine in ME strips from uteri at the 16th day of pregnancy and attenuated significantly, the magnitude of the positive inotropism evoked by the amine. Similar findings were observed in the presence of chlorpheniramine (at 10(-6) M), another H1-receptor blocker. In addition, the positive uterine inotropism evoked by histamine in the ME region of preparations isolated at the 16th day of pregnancy, was significantly reduced by an antagonist of phospholipase A2 (mepacrine, 10(-4) M) as well as by acetylsalicylic acid (ASA at 10(-4) M), an inhibitor of cyclooxygenase. Results also indicate that the excitatory uterine inotropism elicited by the agonistic amine in ME strips isolated from rats at the 16th day of pregnancy, was coincident with an enhanced release of prostaglandins (PGs) E2 and F2 alpha, but not of PGE1 and that both augmenting actions of histamine were antagonized by histamine H1 receptor-blockers, namely pyrilamine (mepyramine or chlorpheniramine. Results suggest that histamine at early pregnancy diminished myometrial inotropism via its interaction with H2-receptors, whereas from mid pregnancy up to the moment of parturition it evokes contractile stimulation, most likely due to the activation of H1-receptor located at the mesometrial region of rat uterine horns.(ABSTRACT TRUNCATED AT 400 WORDS)