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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 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 effects of exogenous histamine (H) on prostaglandin (PG) generation and release in uteri isolated from diestrous rats and the influences of H2-receptors blockers (cimetidine and metiamide) on the output of uterine PGs, were explored. Moreover, the action of H on the uterine 9-keto-reductase, was also studied. Histamine (10(-4) M) failed to alter the basal output of PGE1 but reduced significantly the generation and release of PGE2 and augmented the output of PGF2 alpha. On the other hand, cimetidine (10(-5) M) enhanced the basal release of PGE2 but had no action on the outputs of PGs E1 or F2 alpha. The enhancing effect of H on the production and release of PGF2 alpha was abolished in the presence of cimetidine. Also, the antagonist reversed the influence of H on the output of PGE2. Metiamide, another H2-receptor antagonist, did not alter the basal control generation and release of uterine PGs, but antagonized the augmenting influence of H on PGF2 alpha uterine output, as much as cimetidine did, and prevented the depressive action of H on the release of PGE2 from uteri. Histamine (10(-4) M) significantly stimulated uterine formation of cyclic-adenosine monophosphate, an action which was antagonized by the presence of cimetidine (10(-5) M), a blocker of H2 receptors. Also, histamine (10(-5) M) and dibutyrylcyclic-adenosine monophosphate (DB-cAMP) at 10(-3) M, enhanced significantly the formation 3H-PGF2 alpha from 3H-PGE2. Results presented herein demonstrate that H is able to diminish the generation of PGE2 in uteri from rats at diestrus augmenting the synthesis of PGF2 alpha, apparently via the activation of H2-receptors, enhancing adenylate-cyclase. These effects appear to increase uterine 9-keto-reductase activity which transforms PGE2 into PGF2 alpha. Relationships between the foregoing results and those evoked by estradiol, are also discussed.

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.

The existence of angiotensin I converting enzyme (CE) activity in isolated sow Fallopian tubes and the "in vitro" influences of exogenous bradykinin (BK) on the spontaneous motility of sow oviducts, were explored. Independently of the stage of the sex cycle, the ampullary region of sow Fallopian tubes presented a higher basal CE activity than the isthmic one. On the other hand a greater CE activity was found in the isthmus at estrus and metestrus than at proestrus. Acetylsalicylic acid and mefenamic acid, two inhibitors of prostaglandin synthesis, reduced the CE activity only in ampullary segments obtained at metestrus. BK (0.06 microgram.ml-1) stimulates the spontaneous contractions of isthmic and ampullary tubal segments, triggering tonic responses. The positive inotropism had a longer duration in the isthmus than in the ampulla; presented at estrus a higher magnitude than at proestrus and was enhanced by captopril (50 microgram.ml-1). The data suggest that the low CE activity found in the isthmic tubal region could be subserving the positive inotropic action of BK in the isthmus, long lasting in comparison to that evoked in the ampulla. Moreover, at metestrus some tissue eicosanoid might be modulating the CE activity of ampullary tubal segments. Alternatively the foregoing results could be explained assuming the presence of a carboxy-peptidase different than CE in one region of the oviducts and not in the other, i.e., either one with different sensitivity towards sex hormones and prostaglandin synthesis blockers.