RESUMO
The influence of histaminergic sites in the preoptic-anterior hypothalamic area (POA-AHA) on the basal release of luteinizing hormone (LH) under a continuous regimen of estradiol, progesterone, or both was studied in ovariectomized rats. Different groups of animals were subjected to the following experimental schedule: at day 1, rats received a s.c. silastic implant filled with oil, estradiol, progesterone, or estradiol plus progesterone. Seven days later (day 7), animals were implanted into the POA-AHA with microinjection cannulae. At day 8 and 9, the different groups of rats were microinjected with 1 microliter of saline solution containing 35 nMol of pyrilamine or metiamide, or 20 nMol of alpha-fluoro-methyl-histidine. At day 10, blood samples were taken through a permanent jugular cannulae implanted in situ the day before. LH concentrations were determined in plasma by RIA. Results showed that the increase of LH plasma levels induced by the ovariectomy was inhibited by the estrogen implant, as expected. Treatment of metiamide or alpha-fluoro-methyl-histidine did not affect the pattern of LH secretion. Nevertheless, treatment of metiamide induced a transient increase in the gonadotropin concentrations that extended for two hours (16:00 and 17:00 H). No change in LH plasma levels was observed in rats bearing the progesterone implant. Treatments (pyrilamine, metiamide, or alpha-fluoro-methyl-histidine into the POA-AHA) had no effect. The transient increase in the hormone levels observed in rats treated with pyrilamine in the estrogen-implanted rats was absent in rats bearing the estrogen-progesterone implant.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Estradiol/farmacologia , Histamina/fisiologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Hipotálamo Anterior/efeitos dos fármacos , Hormônio Luteinizante/metabolismo , Adeno-Hipófise/metabolismo , Progesterona/farmacologia , Receptores Histamínicos/fisiologia , Animais , Interações Medicamentosas , Feminino , Metilistidinas/farmacologia , Metiamida/farmacologia , Ovariectomia , Pirilamina/farmacologia , Ratos , Taxa Secretória/efeitos dos fármacosRESUMO
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.
Assuntos
Diestro/metabolismo , Estro/metabolismo , Histamina/farmacologia , Hidroxiprostaglandina Desidrogenases/metabolismo , Prostaglandinas/biossíntese , Receptores Histamínicos H2/efeitos dos fármacos , Útero/metabolismo , Animais , Cimetidina/farmacologia , AMP Cíclico/metabolismo , Estradiol/metabolismo , Feminino , Técnicas In Vitro , Metiamida/farmacologia , Ratos , Ratos EndogâmicosRESUMO
The aim of the present research was to evaluate the histaminergic regulation of prolactin secretion in the lactating rat and the possible involvement of H1 and H2 histamine receptors in this control. Prolactin was measured by radioimmunoassay in blood samples withdrawn through an intrajugular silastic catheter from undisturbed lactating mothers 10 to 15 days after delivery. In some of those rats a stainless steel cannula was placed in the third ventricle. The tested drugs, H1 and H2 receptor agonists and antagonists, were injected either by the intrasilastic route or intraventricularly immediately before the onset of suckling and after a basal sample was taken. New samples were withdrawn 10, 20, 30 and 60 min thereafter. Suckling caused a 12- to 18-fold increase in serum prolactin by 10 min in control saline-injected mothers. In non-suckled mothers (NSM) injected with saline, prolactin levels were low at all times. Systemic or intraventricular diphenhydramine and mepyramine, H1 receptor antagonists, suppressed the increment in prolactin observed in suckled mothers (SM). Intraventricular metiamide, an H2 receptor antagonist, did not modify prolactin secretion in SM but drastically increased serum prolactin in NSM. A small but significant increase in prolactin titers was observed in NSM injected intraventricularly with histamine. 4-Methylhistamine, an H2 agonist, was ineffective when used intraventricularly in NSM, but clearly suppressed prolactin enhancement in SM. It is postulated that in lactating mothers, brain histamine has a dual control on prolactin secretion. H2 receptors mediate events related to inhibition of prolactin release, since the agonist 4-methylhistamine blocked the prolactin rise in SM, while the antagonist metiamide promoted release of the hormone in NSM. H1 receptors seem to be related to a facilitatory mechanism since classical antihistamines suppress the serum prolactin increase that follows the onset of suckling, while histamine itself is able to release prolactin in NSM.