Morphine diminishes the constancy of spontaneous uterine contractions, antagonizes the positive inotropic effects of prostaglandin E2, but not of prostaglandin F2α and inhibits prostaglandin E and F outputs from the uterus of ovariectomized rats

The effects of morphine on the constancy of spontaneous contractions (isometric developed TENSION = IDT and contractile FREQUENCY = CF), in uterine strips isolated from ovariectomized rats and the influence of naloxone, were explored. The inotropic responses to added prostaglandins (PGs) E₂ and F_2α and the influences of morphine and of morphine in the presence of naloxone on PG actions, were also determined. Moreover, the synthesis and outputs of PGs E and F from uteri and the effects of morphine alone and of morphine plus naloxone, were studied. Morphine (10⁻⁶ M) significantly depressed uterine constancy of IDT during the first hours following delivery, but its action on CF did not differ from controls. Naloxone, neither at 10⁻⁸ M nor at 10⁻⁶ M, altered the negative inotropoic influence of morphine on IDT. Exogenous PGs E₂ and F_2α, stimulated uterine inotropism in a concentration-dependent fashion. Morphine altered dose-response curves for exogenous PGE₂, evoking a parallel surmountable shift to the right, but did not affect the inotropic action of added PGF_2α. This antagonistic effect of the opioid was not altered by preincubation with naloxone. Basal synthesis and outputs of PGs E and F in uteri from ovariectomized rats were significantly depressed by morphine (10⁻⁶ M) but not altered by incubating tissues with morphine in presence of naloxone. Results are discussed in terms of a presumptive dual action of morphine on uterine motility, i.e., antagonizing PGE₂ receptors and inhibiting the synthesis of some PGs by the uterus. These influences of morphine do not appear to be subserved by the activation of μ opioid receptors. Moreover, the possibility that endogenous opioids could play a relevant role modulating uterine PG influences, is also discussed.     

Effects of beta-endorphin on spontaneous uterine contractions. Prostaglandins production and 45Ca2+ uptake in uterine strips from ovariectomized rats.

The effects of beta-endorphin, Met-enkephalin, dynorphin and SKF 10047 on the constancy of the isometric developed tension (IDT) of the spontaneous contractions of uterine strips isolated from ovariectomized rats were explored. beta-endorphin (10(-6) M) was the only opioid that depressed significantly uterine constancy of IDT in a concentration dependent fashion. Naloxone, neither at 10(-8) M nor at 10(-6) M, altered the negative inotropic influence of beta-endorphin. Moreover, the basal synthesis and outputs of some prostaglandins (PGE1, PGE2 and PGF2 alpha) from rat uteri and the effect of beta-endorphin (10(-6) M), were determined. It was found that the basal synthesis and release of PGs in uteri were significantly inhibited by this endogenous opioid. The effects of beta-endorphin (10(-8), 10(-6) and 10(-5) M) on the basal; and oxytocin or A23187, induced 45Ca2+ uptake, as well as the influence of naloxone were also studied. beta-endorphin at three of the concentrations tested decreased basal uterine 45Ca2+ uptake and this action was not prevented by naloxone (10(-8) M). The presence of oxytocin and of A23187 augmented significantly 45Ca2+ uptake, an effect that was antagonized by beta-endorphin (10(-6) M). The possible role of beta-endorphin in uterine functioning via the modulation of uterine PG synthesis and Ca2+ uptake is discussed.     

Gamma-linolenic acid improves the constancy of contractions in uteri from sprayed rats and is metabolized to prostaglandin E1 but not to bisenoic prostanoids

The effects of gamma-linolenic acid (GLA) on the time-dependent constancy of spontaneous contractions (isometric developed tension = IDT and frequency of contractions = FC) in uterine strips isolated from spayed rats, were explored. Moreover, the influence of the unsaturated fatty acid on the basal generation and release of tissue prostaglandins (PGs) as well as the conversion of labelled GLA into prostanoids by the uterine tissue and the effects of p-bromo-phenacyl-bromide (BPB), were also studied. GLA (10(-7)M), attenuated significantly the spontaneous decrement of contractile constancy exhibited by control preparations during a period of 180 min of activity in isolation, whereas BPB (10(5) M) resulted in an augmented and faster decrement of inotropic constancy. Spontaneous changes in the constancy of uterine motility as time progressed involved similarly both IDT and FC. After 180 min of activity in isolation a basal generation and release of PGs E and F of the series 1 and 2, were detected. The challenge with 10(-7) M GLA (delivered immediately after isolation) enhanced significantly the output of PGE1 but did not influence the generation and release of PGE2 or PGF2 alpha. BPB (10(-5) M) had no significant effect on the basal output of PGE1, PGE2 or PGF2 but completely prevented the enhancing action of GLA on the synthesis and release of PGE1. Labelled GLA was mainly converted to PGE1 by rat uterine segments and negligible counts in the 2-series of prostanoids, were observed. In presence of BPB (10(-5) M) the conversion of 1-14C-GLA, to PGE1 was almost completely abolished. The foregoing evidences suggest that exogenous GLA is metabolized by the spayed rat uterus via an elongase, forming di-homogamma-linolenic acid (DHLA), which in turn is substrate for cyclo-oxygenase peroxidase reactions yielding finally PGE1. No evidence of a delta 5-desaturase activity, converting DHLA into arachidonate and further derivatives, was detected. Coincidently, exogenous GLA was able to support a better contractile constancy as a function of time than that evidenced in untreated uterine strips isolated from castrated rats.     

Oxytocin enhances the basal release of uterine prostaglandin F2 alpha, but not that of PGE1, or of PGE2, and changes the metabolism of exogenous arachidonate, favouring 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 PGF2 alpha. The in vitro presence of oxytocin (50 mU/ml) increased significantly (p 0.05) the output of PGF 2 alpha 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 less than 0.005) than preparations from non-injected animals, whereas the output of PGF2 alpha 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 PGF2 alpha (p less than 0.001) without changing that of PGs E1 or E2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histamine alters prostaglandin output from diestrous rat uteri. Involvement of H2-receptors and 9-keto-reductase

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.     

Effects of experimental diabetes on spontaneous contractions, on the output of prostaglandins and on the metabolism of labelled arachidonic acid, in uteri isolated from ovariectomized rats. Influences of estradiol

Spontaneous changes in isometric developed tension (IDT) as a function of time after isolation (contractile constancy) in uteri from control-castrated and castrated chronic streptozotocin-diabetic rats, were explored. The effects of injecting 17-beta estradiol (Eo) were also studied. No differences in the minor changes of contractile constancy, between control and diabetic preparations, during a period of 60 min, were detected, whereas uteri from non-diabetic Eo injected animals (0.5 + 1.0 ug, prior to sacrifice), exhibited a profound reduction of IDT, significantly greater than in tissues obtained from Eo injected-diabetic rats. Moreover, basal generation and outputs into the suspending solution of prostaglandins (PGs) E1, E2 and F2 alpha, were explored in the same groups, at 60 min following tissue isolation. The basal outputs of these three PGs were similar in castrated control rats, but preparations from castrated-diabetics released significantly more PGE1. The administration of Eo to castrated-diabetics, failed to alter the releases of the three PGs explored. In addition, the metabolism of labelled arachidonic acid (AA) into different prostanoids (6-keto-PGF1, PGF2, PGE2 and thromboxane B2-TXB2), was also investigated. The non-diabetic spayed rat uterus converted AA into these four prostanoids, the transformation into 6-keto-PGF1 alpha (as an index of PGI2 formation) being the most prominent. In preparations from diabetic rats the formation) being the most prominent. In preparations from diabetic rats the formation of 6-keto-PGF1 alpha, PGF2 alpha and PGE2, was significantly smaller than in controls, whereas a greater % of TXB2 formation (as an index of TXA2), was detected. On the other hand uterine preparations from non-diabetic spayed rats injected with Eo formed less 6-keto-PGF1 alpha and PGE2 and similar amounts of PGF2 alpha or of TXB2 from AA, than Eo injected controls, whereas uteri from castrated diabetic animals injected with Eo, formed a similar % of 6-keto-PGF1 alpha, PGF2 alpha and PGE2 from AA, than tissue preparations from non-estrogenized controls. However, the enhanced transformation of the labelled fatty acid precursor (AA) into TXB2 in the diabetic group, was significantly reduced by the steroid. The role of the augmented generation and release of PGE1 in uteri from diabetic rats is discussed in terms of precedents indicating the relevance of PGs type E supporting rat uterine motility. In addition the influence of Eo is attractive, because its reducing effect on TX production, in diabetes, a disease known to be accompanied by enhanced synthesis of vasoconstrictor and platelet aggregation TXA2, and by frequent obstructive circulat     

Factors subserving the enhancing effect of progesterone on the output of prostaglandin F2 alpha in uteri from ovariectomized rats

The effects of progesterone (P4) and of calcium-ionophore A-23187, on the release of prostaglandins (PGs) E2 and F2 alpha, in uteri isolated from ovariectomized rats and the influences of mepacrine and nifedipine, were explored. The metabolism of labelled arachidonic acid (AA) into different prostanoids (6-keto-PGF 1 alpha, PGE 2 and PGF2 alpha) in uterine segments from spayed rats, injected or not with P4, was also studied. In all cases ovariectomy was performed 20-25 days prior to sacrifice. One group of spayed rats were injected with 4.0 mg of P4 during two days and sacrificed 24 h after the last injection. The remaining spayed animals were considered as controls. Tissue samples from both groups were incubated for one hour in the absence or in the presence of either A-23187 (1.0 microgram/ml), mepacrine (10(-3) M) or nifedipine (10(-6) M), or a combination of A-23187 plus mepacrine. At the end of the incubating period PGs in the suspending solution were extracted, separated, identified (TLC) and quantitated. The metabolism of 14C-AA into different prostanoids was explored in uterine segments from spayed rats, injected or not with P4 prior to sacrifice. Tissue prepared from P4-injected rats as well as those from rats not receiving P4 but incubated with ionophore A-23187, generated and released significantly more PGF2 alpha into the incubating solution than basal controls, but failed to exhibit changes in the basal output of PGE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of morphine on arachidonic acid metabolism, on Ca2(+)-uptake and on cAMP synthesis in uterine strips from spayed rats

The effects of morphine on arachidonic acid metabolism, on cAMP levels and on basal and induced 45Ca2(+)-uptake, in uterine strips isolated from ovariectomized rats as well as the influence of naloxone, were explored. The presence of morphine (10(-6) M) did not change significantly 14C-arachidonic acid metabolism, basal cAMP levels, or cAMP increment induced by PGE2 or by PGE1. On the other hand morphine (10(-6) M) decreased basal uterine 45Ca2(+)-uptake as much as verapamil (10(-6) M) did, and this action was not prevented by naloxone (10(-8) M). The presence of oxytocin (50 mU.ml-1) augmented 45Ca2(+)-uptake, an effect which was antagonized by morphine (10(-6) M). This inhibitory action of morphine on oxytocin-induced 45Ca2(+)-uptake was not prevented by naloxone (10(-8) M). Furthermore, PGE1 (10(-8) M and (10(-6) M) but not PGE2 (10(-8) and 10(-6) M), stimulated the incorporation of 45Ca2+ into uterine strips, and this action was not altered by morphine. The inhibitory influence of morphine on uterine spontaneous motility and on prostaglandin synthesis and release, previously described by us, is now explained in terms of an inhibition of tissue Ca2(+)-uptake.     

Effects of analogues of prostaglandin E2 and F2 alpha on the decidual cell reaction in the rat

The identity of the prostaglandins (PGs) involved in the decidual cell reaction is uncertain. In the present study we investigated the ability of analogues of PGE2 and PGF2 alpha, 16,16-dimethyl-prostaglandin E2, methyl ester (16,16Me2PGE2) and 15(S)-15-methyl-prostaglandin F2 alpha (15MePGF2 alpha) respectively, to bring about decidualization when infused into the uterine lumen of rats sensitized for the decidual cell reaction. As indicated by uterine weights 5 days after the commencement of the infusions into rats in which endogenous PG production had been inhibited by treatment with indomethacin, 16,16Me2PGE2 produced decidualization which was equivalent to that produced by PGE2. By contrast, the infusion of 15MePGF2 alpha inhibited decidualization, even when PGE2 was infused concomitantly. As indicated by uterine radioactivity concentrations after i.v. administration of 125I-labeled bovine serum albumin, the PGF2 alpha analogue also inhibited the endometrial vascular permeability increase which precedes decidualization. Compared to PGE2, 16,16Me2PGE2 was slightly less effective at displacing 3H-PGE2 from an endometrial membrane preparation; by contrast 15MePGF2 alpha was considerably less effective. These data suggest that PGE2 mediates the decidual cell reaction, and that the decidualization obtained in response to PGF2 alpha may involve its conversion within the uterus to PGE2.     

Effects of indomethacin, prostaglandin E2, prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha on hatching of mouse blastocysts

The present study has been performed to investigate how PGs would participate the hatching process. Effects of indomethacin, an antagonist to PGs biosynthesis, on the hatching of mouse blastocysts were examined in vitro. Furthermore, it was studied that prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) or 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were added to the culture media with indomethacin. The hatching was inhibited by indomethacin yet the inhibition was reversible. In the groups with indomethacin and PGE2, no improvement was seen in the inhibition of hatching and the inhibition was irreversible. In the groups with indomethacin and PGF2 alpha, inhibition of hatching was improved in comparison with the group with indomethacin. In the groups with indomethacin and 6-keto-PGF1 alpha, no improvement was seen. The above results indicated that PGF2 alpha possibly had an accelerating effect on hatching and a high concentration of PGE2 would exert cytotoxic effect on blastocysts.     

Differential effects of prostaglandin F2 alpha and of prostaglandins E1 and E2 on cyclic 3',5'-monophosphate production and intracellular calcium mobilization in avian uterine smooth muscle cells

The effects of prostaglandins (PGs) E1 (PGE1), E2 (PGE2) and F2 alpha (PGF2 alpha) on cyclic 3',5'-adenosine monophosphate (cAMP) production and intracellular Ca mobilization were examined in smooth muscle cells of chicken uterus grown in primary culture. At subnanomolar concentrations, both PGE1 and PGE2 significantly suppressed cAMP levels. However, at higher concentrations (0.1-100 microM), both agonists caused a dose-related increase in cAMP production. PGF2 alpha, on the other hand, had no effect on cAMP production. Forskolin (1-100 microM), which also stimulated cAMP production in a dose-dependent fashion, potentiated the effects of both PGE1 and PGE2. In digitonin-permeabilized uterine cells preloaded with 45Ca2+, the addition of PGF2 alpha caused a biphasic 45Ca2+ efflux. There was a small but significant 45Ca2+ release (10.0 +/- 1.5%) within 30 s (rapid phase), followed by a larger one (32.0 +/- 2.0%) within 5 min (slow phase). PGE2, at doses above 1 nM (which significantly increased cAMP accumulation), promoted 45Ca2+ sequestration. This action of PGE2 was observed as early as 1 min and was complete by 5 min. In addition, 0.001 nM PGE2 (a dose that was ineffective on 45Ca2+ mobilization) enhanced PGF2 alpha-induced 45Ca2+ mobilization from 22.5 +/- 5% to 57.0 +/- 3.5%. These results show that PGs of the E series have distinctly different effects on cAMP production and intracellular Ca mobilization. PGF2 alpha action may be linked directly to intracellular Ca mobilization, whereas the effects of PGE may be exerted at multiple sites depending on its local concentration. At low concentrations, its action may be mediated by the suppression of cAMP levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of enzymes of cyclooxygenase pathway and secretion of prostaglandin E2 and F2alpha by porcine myometrium during luteolysis and early pregnancy

Past studies of uterine prostaglandin (PGs) and pig reproduction have focused on endometrial rather than myometrial PGs. This study documents the synthesis and secretion of myometrial prostaglandins (PGs) in pigs and the involvement of oxytocin (OT) in these processes. Cyclooxygenase-2 (COX-2) expression was similar in myometrial explants from cyclic and pregnant pigs (days 14-16) and OT (10(-7) M) in vitro significantly increased COX-2 protein regardless of reproductive state. Basal expression of prostaglandin E2 synthase (PGES) was higher during pregnancy than during luteolysis. Conversely, prostaglandin F synthase (PGFS) was highest during luteolysis and lower in myometrium from gravid animals. OT had no influence on the expression of PGES and PGFS. In another tissue culture experiment, myometrial slices produced more PGE2 than PGF2alpha regardless of reproductive state of the female. OT stimulated PGE2 production in myometrium harvested during luteolysis and increased PGF2alpha production in all tissues examined. Progesterone (P4; 10(-5) M) blocked stimulatory effect of OT on myometrial PG release. Myometrial OTr mRNA was higher (P=0.03) during luteolysis than during pregnancy. In conclusion: (1) oxytocin increases myometrial COX-2 expression, but does not influence the expression of terminal enzymes of PGs synthesis (PGES and PGFS); (2) porcine myometrium preferentially produces PGs during early pregnancy and secretes more PGE2 than PGF2alpha; (3) myometrial OT and OTr support secretion of PGs from myometrium during luteolysis.     

Modulation by opiates of small intestinal prostaglandin E2 and 3',5'cyclic adenosine monophosphate levels and of indomethacin-induced ulceration in the rat.

We studied the effect of parenteral morphine and naloxone administration on intestinal mucosal Prostaglandin E2 (PGE2) and 3',5' cyclic adenosine monophosphate (cAMP) levels and on indomethacin-induced intestinal ulceration in the rat. Compared to the control group, morphine significantly decreased whereas naloxone markedly increased both PGE2 and cAMP mucosal levels, respectively. Morphine or naloxone alone did not cause mucosal injury. However, when given with indomethacin, morphine significantly potentiated the ulcerogenic effect of indomethacin while naloxone exerted a protective effect. These results suggest that opioid peptides may play a role in modulation of intestinal mucosal PGE2 and cAMP levels. In addition, enhancement of indomethacin-induced ulcer formation by morphine and amelioration by naloxone might be in part mediated through their effect on mucosal PGE2 and cAMP levels.     

Effect of chronic alcohol consumption on rat uterine spontaneous motility, prostaglandin production and triglyceride metabolism

The spontaneous isometric developed tension (IDT), the synthesis and release of prostaglandins (PGs) into the incubating medium and the metabolism of triglycerides (TGs) in uterine strips isolated from controls and chronic ethanol fed rats, were studied. In order to observe how the uterus of rats fed alcohol reacts during a situation of metabolic emergency, the above mentioned studies were done in the presence or in the absence of glucose in the incubating medium. The decrement of IDT as time progressed was significantly greater in strips obtained from rats which had been drinking 20% ETOH than in controls. Nevertheless, the absolute magnitude of the initial IDT was similar in both groups. On the other hand, the decline of the frequency of contractions (FC) of uterine strips isolated from controls and from ETOH-exposed rats, after 60 min of spontaneous activity was similar. When the uterine strips isolated from ETOH-exposed and from control rats were suspended in glucose-free solution they exhibited the same decrement of IDT and FC after 60 min of activity. The basal release of PGE1 and PGE2 was similar in control tissues incubated in medium containing glucose, but the output of PGE2 was significantly smaller than that of PGE1 in uterine strips isolated from ETOH-exposed rats. The production of PGE1 and PGE2 by uteri suspended in glucose-free medium was similar in control preparations. On the contrary the release of both PGs differs in uterine strips from ETOH-exposed rats, i.e. the output of PGE2 was significantly smaller than in controls and the release of PGE1 increased around 4-fold in comparison with controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Different responses to prostaglandin F2 alpha and E2 in human extra- and intramyometrial arteries

Tubal segments of the ascending uterine arteries and of intramyometrial arteries were obtained from 18 women who underwent hysterectomy at various phases of the menstrual cycle. Ring preparations of the vessels were mounted in organ baths and isometric tension was recorded. In extramyometrial arteries (outer diameter 2-3 mm) prostaglandin (PG) F2 alpha most potently, but also PGE2 caused concentration-related contractions. In contrast, the contractant effects of both PGs on intramyometrial arteries (outer diameter 0.5-0.6 mm) were negligible. Both extra- and intramyometrial vessels were relaxed to a moderate degree (10-25%) by low concentrations of PGF2 alpha and PGE2. No significant differences between the responses to vasopressin and noradrenaline were found between the vessel preparations. Thus human uterine arteries seem to change their responses to PGF2 alpha and PGE2 as they enter the myometrium and decrease in diameter, and the results raise doubt about the view that direct vasoconstrictor effects of these PGs contribute to the regulation of myometrial blood flow. Such effects of vasopressin and noradrenaline cannot be excluded.     

Prostaglandin E2 and F2 alpha in mid-pregnant rat uterus and at parturition

Prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha) produced by 15 days pregnant rat myometrium, by parturient rat myometrium and myometrium plus endometrium were measured in vitro. The results showed that the PGs produced by parturient myometrium were higher than these obtained during mid-pregnancy. Myometrium with endometrium released more PGs than myometrium alone, and the addition of arachidonic acid (AA) at 10 DM did not show any significant effect. Exogenous progesterone or estradiol-17b at a concentration of 1 Dmol had no effect on parturient uterine PG secretions.     

Influences of estradiol and of catechol and non-catechol estrogens on the output of prostaglandins in uteri from spayed rats

The effects of 17-beta estradiol and of some catechol and non-catechol-estrogens on the synthesis and output of prostaglandins (PGs) E and F by uteri from ovariectomized rats, were explored. Uteri from castrated animals released twice as much PGE than PGF. When uterine tissue was obtained from spayed rats injected prior to sacrifice with a low dose of 17-beta estradiol (0.5 + 1.0 microgram, on two consecutive days), the output of PGE diminished significantly. With a higher dose of the hormone (0.5 + 50.0 micrograms) the depressive influence on the synthesis and release of PGE was even more marked, whereas the output of PGF rose significantly. Low or high doses of estrone or of estriol failed to affect the release of either one of the PGs determined. On the other hand, 2-0H-estradiol at a low dose had no action but at a higher one inhibited the release of PGE without influencing PGF. Neither low nor high doses of 2-0H estriol or of 2-0H estrone affected the synthesis and release of uterine PGs. It was also observed that all the compounds tested evoked a significant uterotrophic action. It appears plausible that some catechol metabolites of 17-beta estradiol, but not other catechol-estrogens, could be involved in the mechanism of action of 17-beta estradiol modulating the production of PGs by the rat uterus.     

A novel anti-lipolytic action of norepinephrine in uteri isolated from spayed rats appears subserved by the activation of alpha 1-adrenoreceptors diminishing the generation and release of lipolytic prostaglandins

The effects of norepinephrine (NE: 3 x 10(-6) M) on the outputs of prostaglandins (PGs) E1, E2 and F2 alpha, from uterine horns isolated from ovariectomized rats and suspended in solutions with or without exogenous glucose, were explored. The releases of the different PGs into the external medium were determined after incubating for one hour uterine preparations, mounted within a tissue bath and receiving a constant preload tension. In glucose-containing solutions, NE enhanced the basal output of PGE2 and failed to alter the basal releases of PGE1 or of PGF2 alpha. In glucose-free media, the basal output of PGE2 was comparable to that detected in presence of exogenous glucose, and its augmentation following added NE was again evident. However, the basal outputs of PGE1 and of PGF2 alpha, greater in glucose-free solutions than in glucose-containing media, were significantly diminished by added NE. Uterine triglyceride (TG) levels were also explored, both immediately after sacrifice (0 min) or following suspending uterine segments during one hour (60 min) in solutions containing exogenous glucose or not. In glucose-containing media, tissue TGs did not differ at 0 min or at 60 min, neither in controls, nor in NE-challenged preparations, whereas in glucose-free solutions, TGs were significantly smaller at 60 min than at 0. interestingly, the addition of NE completely prevented the dimunition of uterine TGs, present at 60 min in glucose-free medium. Neither propranolol nor yohimbine (10(-6) M) altered this sparing action of added NE on tissue TGs, but phentolamine or prazocin (10(-6) M), effectively antagonized the preventive effect of the agonist.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ovarian steroids and oxytocin on the production of prostaglandin E2, prostaglandin F2alpha and endothelin-1 from cow oviductal epithelial cell monolayers in vitro.

Cyclic physio-anatomical variation in the oviducts is mediated by the local countercurrent transfer of ovarian products. Thus, in this study cow oviductal epithelial cells (COEC) culture were utilized to investigate the effects of ovarian products such as progesterone (P4), estradiol 17beta (E2) and oxytocin (OT) on local oviductal prostaglandin E2 (PGE2), F2alpha (PGF2alpha) and endothelin-1 (ET-1) production. COEC were collected from non-pregnant Holstein cows (n = 8) during the follicular phase and cultured in M199 under standard culture conditions until monolayer formation. Cells in first passage were incubated for 24 or 48 h with P4 (500 ng/ml), E2 (1 ng/ml), OT (10(-9) M) or combination of E2 + P4. Administration of E2 significantly increased the production of PGE2, PGF2alpha and ET-1. However, simultaneous administration of P4 blocked the effect of E2. OT did not show any effect on oviductal productions of either PGs or ET-1. The results of this study show that E2 stimulates PG and ET-1 production by COEC in vitro. Thus, it can be suggested that locally transferred E2 from the ovarian follicles may be important for oviductal contraction and gamete/zygote transport during the peri-ovulatory period.     

The lack of involvement of central nervous system in the antiarrhythmic effects of prostaglandins E2, F2 alpha, and I2 in cat

The role of the central nervous system (CNS) in the antiarrhythmic effects of prostaglandins (PGs) E2, F2 alpha, and I2 was studied by administering each agent into the left lateral cerebral ventricle (i.c.v. administration) of chloralose-anaesthetized cats. The cardiac arrhythmias were produced by intravenous (i.v.) infusion of ouabain (1 microgram/kg/min). The PGs E2, F2 alpha and I2 on i.c.v. administration in the dose range of 1 ng to 10 micrograms failed to inhibit ouabain-induced cardiac arrhythmias. However, when infused i.v., PGE2 (1 microgram/kg/min), PGF2 alpha (5 micrograms/kg/min), and PGI2 (2 micrograms/kg/min) effectively suppressed these arrhythmias. The standard antiarrhythmic drug propranolol (0.5-8.0 mg) on i.c.v. administration also significantly reduced the ouabain-induced cardiac arrhythmias. It is suggested that the CNS is not the site of action of PGs E2, F2 alpha, and I2 in antagonising the ouabain-induced cardiotoxicity in cats.