RESUMO
Glucose transport by uterine strips from ovariectomized estrogenized rats was explored. Sugar transport was significantly different from saccharose values (non-specific diffusion) only after 60 min of incubation. The addition of cytochalasin B demonstrated that we are measuring a specific mechanism for glucose transport. Insulin-enhanced sugar transport only at 0.5 or 0.25 U/ml prostaglandin E1 (PGE1), PGE2 and PGF2 alpha (10(-7) M) significantly improved glucose transport, but indomethacin (10(-6) M) failed in modifying this parameter in either control nor insulin-treated tissues. We did not observe an additive or synergistic action between PGE2 (10(-7) M) and insulin (used at maximal or submaximal concentration).
Assuntos
Alprostadil/farmacologia , Dinoprostona/farmacologia , Glucose/metabolismo , Prostaglandinas F/farmacologia , Útero/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico Ativo/efeitos dos fármacos , Citocalasina B/farmacologia , Difusão , Interações Medicamentosas , Estradiol/farmacologia , Feminino , Indometacina/farmacologia , Insulina/farmacologia , Ovariectomia , Ratos , Ratos Wistar , Estimulação Química , Sacarose/metabolismo , Útero/metabolismoRESUMO
The production of 14CO2 from labelled glucose by isolated uterine strips from ovariectomized-diabetic rats has been studied. U46619, an analogue of TXA2 did not affect basal glucose metabolism; however, insulin-induced increment in CO2 production was completely blocked, both in ovariectomized (OVD) or ovariectomized-estrogenized (OVED) diabetic uterus. OKY064 as well as UK38485, both inhibitors of TXA2 synthesis, stimulated glucose metabolism (p < 0.05) similar to that of insulin in uterine tissue from OVD and OVED rats. Inhibition in the synthesis and release of TXB2 was detected (p < 0.01) by uterine radioconversion of 14C-arachidonic acid when adding OKY38485 to the incubation medium, and the production of other prostanoids such as 6-keto-PGF1 alpha, PGF2 alpha and PGE2 was enhanced. In summary, TXA2 inhibited insulin-induced glucose metabolism in diabetic animals.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Insulina/farmacologia , Endoperóxidos Sintéticos de Prostaglandinas/farmacologia , Tromboxano A2/análogos & derivados , Tromboxano A2/antagonistas & inibidores , Útero/efeitos dos fármacos , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico , Animais , Radioisótopos de Carbono , Estrogênios/metabolismo , Feminino , Imidazóis/farmacologia , Técnicas In Vitro , Ovariectomia , Prostaglandinas/biossíntese , Ratos , Ratos Wistar , Tromboxano A2/biossíntese , Tromboxano A2/farmacologia , Tromboxano-A Sintase/antagonistas & inibidores , Útero/metabolismoRESUMO
We explored the oxytocin-prostaglandin interactions during the rat estrous cycle. The experiments were done with uterine preparations isolated from rats in different stages of the sex cycle incubated 'in vitro' with oxytocin (O) (50 mU/ml). We found that the effect of O on prostaglandin (PG) synthesis was associated to the sex hormones, and varied during the estrous cycle. Indeed, during the estrogenic influence (i.e. at proestrus and estrus) O diminished the synthesis of PGE2 and with the highest estradiol concentration (i.e. during estrus) the hormone also augmented the synthesis of PGF2 alpha. During metestrus, no changes in PG synthesis after treatment were found. Likewise, during diestrus, when progesterone levels fall, O enhanced PGF2 alpha uterine synthesis. In this study an inhibitory action of O on the uterine production of 6-keto-PGF1 alpha at proestrus was also seen. The present results indicate that when estrogen concentration increases (during estrus) 6-keto-PGF1 alpha synthesis also increases. In summary, we have observed that sex hormones exert a modulating action on the influences of O on uterine PGs synthesis.
Assuntos
Estro/fisiologia , Ocitocina/farmacologia , Prostaglandinas/biossíntese , Útero/metabolismo , 6-Cetoprostaglandina F1 alfa/biossíntese , Animais , Ácido Araquidônico/metabolismo , Diestro/fisiologia , Dinoprosta/biossíntese , Dinoprostona/biossíntese , Feminino , Metestro/fisiologia , Proestro/fisiologia , Ratos , Ratos Wistar , Útero/efeitos dos fármacosRESUMO
Spontaneous contractile activity, glucose (Glu), glycogen (GLY), triglyceride (TG) metabolism and eicosanoid production, was evaluated in isolated uterine strips from control and non-insulin-dependent diabetic rats on day 10 of pregnancy. Metabolism of Glu, levels of GLY and TG and eicosanoid production were also studied in day 10 embryos obtained from both experimental groups. "In vitro" isometric developed tension (IDT), was similar at 0 hr in control and diabetic uterine preparations, but IDT was decreased after a 60 min incubation in the diabetic group. The frequency of contractions (FC) was similar at 0 hr and after 60 min incubation in both experimental groups. On the other hand, the production of 14CO2 from U14C-glucose was lower in isolated uteri and embryos obtained from diabetic rats than in controls. Initial TG levels were similar in uteri isolated from control and diabetic rats, and higher in embryos obtained from diabetic mothers than in controls. Levels of TG in uterine strips suspended in Glu or Glu-free medium did not differ at 0 hr or at 60 min either in controls or in diabetic rats. On the contrary GLY levels in uterine strips from diabetic animals were higher than in controls, whereas in embryos from diabetic mothers GLY levels were similar to controls. Levels of GLY in uterine strips from controls and diabetic animals decreased after 60 min incubation only in the absence of Glu in the incubation medium. Production of PGE2, PGE1, 6-keto-PGF1 alpha, PGF2 alpha, TXB2 and LTB4 was studied in uterine strips and embryos obtained from control and diabetic rats. No differences were found between control and diabetic uterine prostanoid production, but lower production of LTB4 was observed in diabetic uteri. However production of PGE2 and PGF2 alpha was greater in embryos obtained from diabetic mothers than in controls. In this study, we observed lower uterine metabolic alterations than in the pancreatectomized diabetic rat model studied previously, but important anomalies in the embryos obtained from non-insulin-dependent diabetic mother were found.
Assuntos
Eicosanoides/biossíntese , Glucose/metabolismo , Glicogênio/metabolismo , Gravidez em Diabéticas/metabolismo , Triglicerídeos/metabolismo , Útero/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Embrião de Mamíferos/metabolismo , Feminino , Técnicas In Vitro , Masculino , Gravidez , Ratos , Ratos Wistar , Contração Uterina , Útero/fisiopatologiaRESUMO
"In vitro" isometric developed tension (IDT) and frequency of contractions (FC), glucose (Glu), glycogen (GLY) and triglyceride (TG) metabolism, as well as prostaglandin PGE2 and PGE1 production, were studied in uterine strips and in embryos isolated from controls and diabetic rats at day 10 of pregnancy. The IDT and the FC, at 0 time or after a 60 min incubation, were not different in controls and in preparations from diabetic animals when the uterine strips were incubated in glucose or in glucose-free medium (p > 0.05). The production of 14CO2 and 14C-lactate from 14C-glucose were lower in the diabetic group than in controls (p < or = 0.05). Indomethacin (10(-6) M), an inhibitor of prostaglandin synthesis, failed to modify these results. Labelled Glu metabolism by isolated embryos was similar (p > 0.05) in controls and in embryos obtained from diabetic mothers. On the other hand, the initial TG and GLY levels were higher (p < or = 0.05) in diabetic uterine tissues than in controls. However, the values of TG and GLY in embryos obtained from both experimental groups were similar (p > 0.05). TG levels in uterine strips suspended in Glu or in Glu-free medium did not differ (p > 0.05) at 0 time (postisolation) and at 60 min, either in controls or in diabetic rats. However, Gly levels in uterine strips from diabetic animals, decreased significantly at 60 min in tissues incubated in Glu or in Glu-free medium (p < or = 0.05). In controls, uterine Gly content decreased (p < or = 0.05) only at 60 min time when the strips were incubated in Glu-free medium. Finally, uterine tissue from controls as well as from diabetic pregnant rats release more PGE2 than PGE1 into the incubation medium (p < or = 0.001). Nevertheless, secretion of PGE2 and PGE1 was similar in both experimental groups and was not modified by the presence or absence of glucose. In summary, we found differences in uterine metabolism of glucose, glycogen and triglycerides in controls and in diabetic rats, but metabolic differences have not been detected between embryos obtained from controls and from diabetic mothers.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Glicogênio/metabolismo , Gravidez em Diabéticas/metabolismo , Prostaglandinas/biossíntese , Triglicerídeos/metabolismo , Alprostadil/biossíntese , Animais , Técnicas de Cultura , Dinoprostona/biossíntese , Feminino , Feto/metabolismo , Indometacina/farmacologia , Lactatos/metabolismo , Ácido Láctico , Gravidez , Ratos , Ratos Wistar , Contração Uterina/fisiologia , Útero/efeitos dos fármacos , Útero/metabolismoRESUMO
Eicosanoid production by uterine strips and by embryos obtained from normal and diabetic rats at day 10 of pregnancy was studied. It was found that the release of 6-keto-PGF1 alpha (representing PGI2 synthesis) and of LTB4 was less in preparations from diabetic animals than in controls. The production of TXB2 (indicating the formation of TXA2) by uterine tissue obtained from diabetic rats was almost double that of controls. The synthesis and release of eicosanoids when tissues were incubated in glucose-containing solution or in glucose-free medium were similar, with the exception of LTB4, which was diminished with uterine strips from diabetic rats. The mean number of embryos in control pregnant rats (12.4 +/- 0.5) and in diabetic mothers (10.1 +/- 1.3) was not significantly different, but in 4 of the 14 diabetic rats studied, all of their embryos were resorbed. Although embryos released large amounts of PGF2 and PGE2, and small amounts of 6-keto-PGF1 alpha, TXB2 and LTB4, the amounts of each eicosanoid in control and diabetic groups were similar. The present results indicate that the diabetic state, which induces alterations in uterine eicosanoid production, do not influence arachidonic metabolism in their corresponding embryos.
Assuntos
Eicosanoides/biossíntese , Embrião de Mamíferos/metabolismo , Gravidez em Diabéticas/metabolismo , Útero/metabolismo , Animais , Feminino , Idade Gestacional , Glucose/farmacologia , Técnicas In Vitro , Gravidez , Ratos , Ratos Wistar , SoluçõesRESUMO
Na(+)-K(+)-ATPase activity has been implicated in the metabolism of arachidonate and the release of prostaglandins (PG). The aim of the present study was to investigate a potential interaction between the activity of this enzyme and the production of bisenoic PG by uteri isolated from spayed rats. Ouabain or the incubation in low K+ medium (conditions which inhibit Na(+)-K(+)-ATPase) diminished the conversion of 14C-arachidonic acid to 6-keto-PGF1 alpha and PGF2 alpha and increased the production of TXB2. The incubation of uterine strips in a high K+ medium (condition which enhances Na(+)-K(+)-ATPase activity) increased the formation and release of 6-keto-PGF1 alpha and PGF2 alpha while the production of TXB2 and PGF2 diminished significantly. These observations suggested that the activity of Na(+)-K(+)-ATPase could modulate the production of PG and that could be involved in the alterations of the metabolism of eicosanoids found in several tissues during diabetes.
Assuntos
Eicosanoides/biossíntese , ATPase Trocadora de Sódio-Potássio/metabolismo , Útero/metabolismo , 6-Cetoprostaglandina F1 alfa/biossíntese , Animais , Ácido Araquidônico/metabolismo , Diabetes Mellitus Experimental/metabolismo , Dinoprosta/biossíntese , Feminino , Técnicas In Vitro , Ouabaína/farmacologia , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Tromboxano B2/biossínteseRESUMO
We attempted to explore possible mechanism(s) subserving the influence of oxytocin (O) and of progesterone (P) in the isolated rat uterus studying the action of these hormones on: the synthesis and release of prostaglandins (PGs), the metabolism of labelled arachidonic acid and the uptake of Ca2+ by the tissue from ovariectomized animals. The experiments were done with uterine preparations isolated from spayed rats treated or not with P prior to sacrifice and afterward incubated or not with O 'in vitro'. While uterine strips from untreated spayed rat uterus exhibited a basal release into the incubating medium of approximately the same amounts of PGF2 alpha, and PGE2, the 'in vitro' addition of O (50 mU/ml) increased significantly (p < 0.05) the output of PGF2 alpha without changing the release of PGE2. In tissue from rats injected with P prior to sacrifice the output of PGF2 alpha rose significantly (p < 0.01) as it did after the addition of O to preparations obtained from spayed rats treated with P in comparison to findings in uteri from spayed rats but not in comparison to uteri from spayed rats treated with P alone. Moreover, the 'in vitro' addition of O (50 mU/ml) only increased the formation of PGF2 alpha (p < 0.05) and of 5-HETE (p < 0.05); nevertheless the administration of P to spayed rats diminished significantly (p < 0.05) the formation of 6-keto-PGF1 alpha from uteri, but increased that of PGF2 alpha (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Ácido Araquidônico/metabolismo , Cálcio/metabolismo , Ocitocina/farmacologia , Progesterona/farmacologia , Útero/efeitos dos fármacos , Animais , Dinoprosta/biossíntese , Feminino , Ovariectomia , Ratos , Ratos Wistar , Útero/metabolismoRESUMO
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.
Assuntos
Cálcio/metabolismo , Prostaglandinas/biossíntese , Útero/efeitos dos fármacos , beta-Endorfina/farmacologia , Animais , Dinorfinas/farmacologia , Encefalina Metionina/farmacologia , Feminino , Técnicas In Vitro , Transporte de Íons/efeitos dos fármacos , Ovariectomia , Fenazocina/análogos & derivados , Fenazocina/farmacologia , Ratos , Ratos Wistar , Contração Uterina/efeitos dos fármacos , Útero/fisiologiaRESUMO
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)
Assuntos
Alprostadil/biossíntese , Dinoprosta/biossíntese , Dinoprostona/biossíntese , Lipase/farmacologia , Fosfolipases A/farmacologia , Útero/efeitos dos fármacos , Ácido 5,8,11,14-Eicosatetrainoico/análogos & derivados , Ácido 5,8,11,14-Eicosatetrainoico/farmacologia , Alprostadil/genética , Animais , Ácidos Araquidônicos/metabolismo , Bradicinina/farmacologia , Dinoprosta/metabolismo , Dinoprostona/genética , Feminino , Fosfolipases A2 , Ratos , Ratos Endogâmicos , Útero/metabolismoRESUMO
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)
Assuntos
Alcoolismo/fisiopatologia , Prostaglandinas/biossíntese , Triglicerídeos/metabolismo , Útero/fisiopatologia , Alcoolismo/metabolismo , Alprostadil/biossíntese , Alprostadil/metabolismo , Animais , Dinoprostona/biossíntese , Dinoprostona/metabolismo , Feminino , Técnicas In Vitro , Prostaglandinas/metabolismo , Ratos , Ratos Endogâmicos , Contração Uterina , Útero/metabolismoRESUMO
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)
Assuntos
Ácidos Araquidônicos/metabolismo , Estradiol/farmacologia , Ocitocina/farmacologia , Útero/metabolismo , Alprostadil/metabolismo , Animais , Cálcio/metabolismo , Dinoprosta/metabolismo , Dinoprostona/metabolismo , Feminino , Ácidos Hidroxieicosatetraenoicos/metabolismo , Indometacina/farmacologia , Contração Muscular/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Útero/efeitos dos fármacosRESUMO
The effects of leukotriene C4 (LTC4), nordihydroguaiaretic acid (NDGA) and FPL-55712, on the metabolism of labelled glucose (U14C-glucose) in uteri isolated from spayed rats and from spayed-estrogenized rats, incubated in the presence and in the absence of indomethacin, were explored. Indomethacin (10(-6)M), enhanced significantly 14CO2 formation from labelled glucose, both in uteri from ovariectomized rats and in uteri from ovariectomized-estrogenized animals. In uteri from spayed not-estrogenized rats, expose 'in vitro' to indomethacin, NDGA (10(-5)M), an inhibitor of the 5-lipoxygenase, as well as FPL-55712 (10(-5)M), a LT antagonist, reduced significantly the enhanced metabolism of glucose evoked by indomethacin, an inhibitor of the cyclo- oxygenase. On the other hand, LTC4 (10(-7)M), augmented the metabolism of labelled glucose, reaching values even greater than those induced by indomethacin. In the spayed-estrogenized group LTC4 (10(-10)-10(-7)M) enhanced the formation of labelled CO2 from labelled glucose as much as indomethacin (10(-6)M) did, whereas neither NDGA nor FPL-55712 were effective. In addition, in uteri from ovariectomized-estrogenized rats, incubated with indomethacin, NDGA and FPL-55712, decreased the augmenting action of indomethacin on glucose metabolism, whereas LTC4 (10(-10)-10(-7)M) evoked a complete reversal of the inhibitory influence of NDGA on the formation of 14CO2. The force-going results suggest that tissue 5-lipoxygenase products, particularly LTC4, are involved in the metabolism of labelled glucose by rat uteri, mainly when the cyclo-oxygenase pathway is inhibited by indomethacin and the tissue is deprived of estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Estradiol/farmacologia , Glucose/metabolismo , Indometacina/farmacologia , SRS-A/farmacologia , Útero/metabolismo , Animais , Dióxido de Carbono/metabolismo , Cromonas/farmacologia , Feminino , Técnicas In Vitro , Masoprocol/farmacologia , Ovariectomia , Ratos , Ratos Endogâmicos , Útero/enzimologiaRESUMO
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.
Assuntos
Estrogênios de Catecol/farmacologia , Estrogênios/farmacologia , Prostaglandinas/metabolismo , Útero/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Estradiol/farmacologia , Estriol/farmacologia , Estrona/farmacologia , Feminino , Ovariectomia , Prostaglandinas E/metabolismo , Prostaglandinas F/metabolismo , Ratos , Útero/metabolismoRESUMO
The effects on ovulation of a specific anti-oxytocin rabbit serum (anti-OT) (50.0 microliters) given by intrabursal injection into the right ovaries of etherized adult female rats at proestrus, were explored by counting the number of ovulated ova present within the right oviducts. Left ovaries were not treated and served as control ovaries. Control rats were treated with male normal rabbit serum (NRS) (50.0 microliters) given by intrabursal injections into the right ovaries of animals at proestrus. Ovulation was induced by injection of human chorionic gonadotrophin (hCG). Anti-OT administered into the right ovarian bursae of proestrous rat ovaries evoked a significant 51% inhibition of ovulation in comparison with that observed in control non-injected left ovaries (p less than 0.01). Also, when the ovulation of right ovaries injected with anti-OT was compared with that of left ovaries injected with NRS, the number of ovulated ova in the right side was significantly smaller (30%) than on the contralateral side (p less than 0.02). However, in rats pre-treated with hCG the intrabursal injection of oxytocin (OT) (50.0 mU/ml) into right and left ovaries failed to alter the number of ovulated ova compared with that of rats receiving intrabursal injections of saline. The basal control and the OT-evoked synthesis and release of endogenous prostaglandin E2 (PGE2) and PGF2 alpha were explored in ovaries isolated from prepuberal rats injected with pregnant mare's serum gonadotrophin (PMSG), two days prior to sacrifice. OT augmented the basal release of PGF2 alpha but did not influence that of PGE2. Moreover, the conversion of exogenous 14C-arachidonic acid (14C-AA) into different prostanoids and into 5-HETE, in the presence and in the absence of added OT (50.0 mU/ml), was studied in rat ovaries isolated in proestrus. The challenge with OT augmented the basal synthesis and release of PGF2 alpha and of 5-HETE from 14C-AA, but failed to influence the formation of products generated via the cyclo-oxygenase pathway, namely 6-keto-PGF1 alpha, PGE2 and thromboxane B2 (TXB2). Therefore, the present results suggest that ovarian OT may play a role in the ovulatory process, via generation of PGF2 alpha to enhance contractions of ovarian smooth muscle and of 5-HETE to promote follicular collagenolysis.
Assuntos
Araquidonato 5-Lipoxigenase/metabolismo , Araquidonato Lipoxigenases/metabolismo , Ovário/enzimologia , Ovulação , Ocitocina/fisiologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Ácido Araquidônico , Ácidos Araquidônicos/metabolismo , Feminino , Ácidos Hidroxieicosatetraenoicos/metabolismo , Técnicas In Vitro , Ovário/efeitos dos fármacos , Ocitocina/imunologia , Ocitocina/farmacologia , Ratos , Ratos EndogâmicosRESUMO
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)
Assuntos
Dinoprosta/análise , Progesterona/farmacologia , Prostaglandinas E/análise , Útero/efeitos dos fármacos , Animais , Ácido Araquidônico , Ácidos Araquidônicos/metabolismo , Calcimicina/farmacologia , Feminino , Nifedipino/farmacologia , Ovariectomia , Quinacrina/farmacologia , Ratos , Ratos Endogâmicos , Útero/metabolismoRESUMO
The effects of prostaglandins (PGs) E1, E2 and F2 alpha on the oxidation of labelled glucose in uterine strips from ovariectomized rats, were explored. Moreover, the influences of in vivo estrogenization of spayed rats and the presence in vitro of indomethacin (10(-6)M) on labelled glucose metabolism by isolated uteri, were also determined. PGE2 (10(-7)M), but not PGE1 or PGF2 alpha, enhanced significantly the formation of 14CO2 from U14C-glucose in uteri from spayed rats. After the injection of 17-beta estradiol to castrated animals prior to sacrifice the three PGs augmentated in vitro uterine glucose metabolism. In uterine strips from spayed non-estrogenized rats incubated with indomethacin, only PGE2 (10(-7) and 10(-6) M) incremented the formation of 14CO2 from labelled glucose, whereas PGE1 and PGF2 alpha were devoid of action, whereas in uteri from ovariectomized-estrogenized animals also incubated with indomethacin, PGE1, PGE2 and PGF2 alpha enhanced significantly the metabolism of labelled glucose, as was observed in the absence of indomethacin. However, in the presence of indomethacin the magnitude of the stimulation evoked by PGs in vitro was 3 to 4 times greater than without the inhibitor of the cyclo-oxygenase. The role of estradiol modulating the actions of PGE2 and PGF2 alpha on uterine glucose metabolism and possible reasons subserving the influence of indomethacin incrementing the effects of PGs on glucose oxidation in uteri from spayed-estrogenized rats, are discussed.
Assuntos
Dinoprostona/farmacologia , Glucose/metabolismo , Útero/efeitos dos fármacos , Alprostadil/farmacologia , Animais , Dinoprosta/farmacologia , Estradiol/farmacologia , Feminino , Técnicas In Vitro , Indometacina/farmacologia , Ovariectomia , Ratos , Ratos Endogâmicos , Útero/metabolismoRESUMO
Bone marrow CFUe mice cultures were prepared in Petri dishes and the number of full developed erythrocyte colonies were counted under various experimental conditions. In certain experiments, erythropoietin (EP = 0.4 U x ml-1 in the suspending medium) or sera from normal rats (100 microliters) or from animals with chronic turpentine sterile abscesses (60 or 100 microliters), were delivered to the CFUe colonies. The number of colonies in the group without EP was almost 5 times smaller than in the group with EP. Inasmuch as some few colonies are still able to develop, even in absence of added EP, the suggestion is advanced holding that the phenomenon may represent the effect of EP already bound to the group of cells initiating differentiation. Comparisons among all experimental groups indicate that the delivery of sera from turpentine rats to cultures containing added EP, reduced significantly the number of CFUe colonies seen in controls with EP but without inflammatory serum. It is suggested that the present findings could be explained assuming an inhibition of the influence of exogenous EP, subserved by the inflammatory serum, or alternatively that this kind of rat serum induces a partial blockade of EP at receptor sites whose activation is a mandatory step for the adequate and full development of cultured erythrocytes.
Assuntos
Abscesso/sangue , Sangue , Células Precursoras Eritroides , Eritropoetina/farmacologia , Terebintina/farmacologia , Abscesso/etiologia , Animais , Células da Medula Óssea , Feminino , Ratos , Ratos EndogâmicosRESUMO
Bone marrow CFUe mice cultures were prepared in Petri dishes and the number of full developed erythrocyte colonies were counted under various experimental conditions. In certain experiments, erythropoietin (EP = 0.4 U x ml-1 in the suspending medium) or sera from normal rats (100 microliters) or from animals with chronic turpentine sterile abscesses (60 or 100 microliters), were delivered to the CFUe colonies. The number of colonies in the group without EP was almost 5 times smaller than in the group with EP. Inasmuch as some few colonies are still able to develop, even in absence of added EP, the suggestion is advanced holding that the phenomenon may represent the effect of EP already bound to the group of cells initiating differentiation. Comparisons among all experimental groups indicate that the delivery of sera from turpentine rats to cultures containing added EP, reduced significantly the number of CFUe colonies seen in controls with EP but without inflammatory serum. It is suggested that the present findings could be explained assuming an inhibition of the influence of exogenous EP, subserved by the inflammatory serum, or alternatively that this kind of rat serum induces a partial blockade of EP at receptor sites whose activation is a mandatory step for the adequate and full development of cultured erythrocytes.
RESUMO
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 F2 alpha 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 inotropic influence of morphine on IDT. Exogenous PGs E2 and F2 alpha, 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 PGF2 alpha. 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 mu opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)