Biomedical subjects

B H Duvilanski

Publications and source records attributed to B H Duvilanski.

At least 19 recordsLinked to original sources

PubMed1998

Nitric oxide donors modify free intracellular calcium levels in rat anterior pituitary cells.

The effect of nitric oxide donors on intracellular calcium concentration [Ca2+]i was studied in anterior pituitary cells using ratiometric FURA 2 fluorescence measurements. Sodium nitroprusside (NP) induced a transient decrease in [Ca2+]i, after which [Ca2+]i returned to, or even increased over basal values. S-Nitroso glutathione (GSNO) induced a similar decrease. NP also inhibited high [Ca2+]i achieved by depolarization with 25 mM K+. The inhibitory effect of NP was partially blunted by pretreatment with methoxy-verapamil, and in calcium free buffer, and was not altered by thapsigargin. Interestingly, in calcium free buffer there was a significant stimulatory effect of NP, which was partially blunted by thapsigargin. We conclude that NO donors modify [Ca2+]i in anterior pituitary cells. The action is biphasic, with an initial decrease in [Ca2+]i probably related to a decrease of Ca2+ influx through VDCC, and an increase evidenced in calcium free buffer in which the inhibitory component is absent, and partially depends on thapsigargin sensitive calcium stores.

Animals↗

PubMed1998

Daily variations of amino acid concentration in mediobasal hypothalamus, in rats injected with Freund's adjuvant. Effect of cyclosporine.

Although the existence of central responses to inflammatory injuries was already reported, the existence of hypothalamic amino acid responses has been less explored. The present study was designed to characterize the 24-h changes in mediobasal hypothalamic excitatory and inhibitory amino acid neurotransmitter contents and to analyze the effect of Freund's complete adjuvant administration on these patterns. Also the effects of the immunosuppressant drug Cyclosporine was studied. The content of aspartate, glutamate, glutamine, GABA and taurine was measured by HPLC with fluorimetric detection. The results show the existence of specific daily rhythms of aspartate, glutamate, glutamine, GABA and taurine contents in the mediobasal hypothalamus of control rats. Maxima for these amino acids was found at midnight, although another peak of lesser magnitude, occurred during the light phase of the photoperiod, except for TAU in which both peaks were of similar magnitude. Freund's complete adjuvant administration did not modify the 24-h pattern of any amino acid studied. It reduced the midnight peak of glutamate, glutamine and GABA and increased that of taurine. Moreover, it increased and extended the midday peak of glutamate. Besides, Freund's adjuvant did not modify aspartate content at any time point studied. Cyclosporine pretreatment did not prevent the inhibitory effects of Freund's complete adjuvant on glutamate, glutamine and GABA midnight peaks. However, the drug blocked the increase in the content of taurine at midnight and increased its midday peak. Moreover, cyclosporine administration abolished the variations of ASP during the scotophase, as compared to control animals and shift delayed both peaks of glutamate. The results indicate the existence of a significant effect of immune-mediated inflammatory response of the mediobasal hypothalamic amino acids studied, at an early phase after Freund's adjuvant administration, and that these changes were partially sensitive to the immunosuppression induced by cyclosporine.

Amino Acids↗

PubMed1998

Effect of lipopolysaccharide on tumor necrosis factor and prolactin release from rat anterior pituitary cells.

TNF-alpha plays a critical role in the cascade of neuroendocrine events during inflammation and septic shock. It also affects the release of pituitary hormones and acts as a growth factor in immune and nonimmune cells. The aim of the present study was to investigate the release of TNF-alpha from rat anterior pituitary cells and the effect of the steroid medium on its release. Cultured anterior pituitary cells from lactating rats spontaneously released TNF-alpha. The presence of lipopolysaccharide (LPS, 0.1 microg/mL) in the culture medium significantly increased TNF-alpha release and inhibited prolactin release. Chronic estrogenization of ovariectomized rats or the presence of 17 beta-estradiol in the culture medium also increased TNF-alpha release. LPS significantly stimulated TNF-alpha release in all groups and abrogated the estrogen-induced prolactin release. We also investigated the effect of TNF-alpha on prolactin release. The presence of TNF-alpha (50 ng/mL) in the culture medium inhibited prolactin release from anterior pituitary cells. These data show that anterior pituitary cells in culture release TNF-alpha and that this release is stimulated by estrogens. Our results also indicate that LPS inhibits prolactin release in an estrogenic environment, suggesting that TNF-alpha could affect pituitary hormone release during endotoxemia.

Animals↗

PubMed1997

Vasoactive intestinal peptide (VIP) mediates the effect of estrogens on the dopaminergic tone in the hypothalamic-pituitary axis of ovariectomized (OVX) rats.

The role of vasoactive intestinal peptide (VIP) in the regulation of dopamine (DA) concentration in mediobasal hypothalamus (MBH), posterior and anterior pituitary of ovariectomized (OVX) estrogenized rats was studied using passive immunization against VIP with a specific antiserum (a-VIP). Chronic estradiol administration decreased DA concentration in MBH, and in posterior and anterior pituitary, compared to OVX control rats. DA tissue concentration increased following a-VIP administration to control and estrogenized OVX rats. In vitro study of VIP and a-VIP on DA release from MBH in chronically estrogenized OVX rats showed that estrogens decreased DA evoked-release from MBH;a-VIP increased DA evoked-release from MBH of control OVX and estrogenized rats. VIP decreased DA evoked-release from MBH of OVX rats, but had no effect on estrogenized rats. VIP decreased DA tissue concentration in MBH of OVX control but not of estrogenized rats. It is suggested that VIP decreases DA synthesis and release from hypothalamic neurons in female rats, and that VIP partially mediates the inhibitory effect of long-term estrogen administration on DA release from MBH.

Animals↗

PubMed1996

Role of nitric oxide/cyclic GMP pathway in the inhibitory effect of GABA and dopamine on prolactin release.

The anterior pituitary gland is a site of nitric oxide (NO) production and action, suggesting a local regulatory function. We recently reported that NO inhibits in vitro prolactin release. The aim of the present study was to establish the mechanism of action of NO on prolactin release and to determine whether NO is involved in the inhibitory effect of GABA on prolactin release. Since NO exerts its action through cGMP by activating guanylate cyclase in different tissues, we examined the effect of sodium nitroprusside (NP), a NO releaser, on intrapituitary cGMP levels. Incubation of anterior pituitary glands with 0.5 mM NP 4-fold increased intrapituitary cGMP content, but decreased intrapituitary cAMP levels. In addition, we studied the effect of NP on prolactin release in the presence of LY 83583, an inhibitor of guanylate cyclase activity and 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase activity. 10 microM LY 83583 and 0.5 mM IBMX blocked the inhibitory effect of NP on prolactin release. (10(-3) M) 8Br-cGMP, an analogue of cGMP, mimicked the effect of NP on prolactin release. On the other hand, NO seems to be involved in the inhibitory effect of GABA on prolactin release since hemoglobin, a scavenger of NO, and Nw-nitro-L-arginine methyl ester, an inhibitor of NO synthase (NOS), blocked the pituitary response to GABA. Moreover, GABA (10(-6) M) stimulated NOS activity by almost 50%. GABA increased intrapituitary cGMP levels and decreased cAMP. Dopamine stimulated NOS activity weakly. These observations suggest that NO, acting through the guanylate cyclase-cGMP pathway, inhibits prolactin secretion. In addition, NO may be involved in the inhibitory effect of GABA and dopamine on prolactin release.

1-Methyl-3-isobutylxanthine↗

PubMed1995

Nitric oxide inhibits the release of norepinephrine and dopamine from the medial basal hypothalamus of the rat.

Previous research indicates that norepinephrine and dopamine stimulate release of luteinizing hormone (LH)-releasing hormone (LHRH), which then reaches the adenohypophysis via the hypophyseal portal vessels to release LH. Norepinephrine exerts its effect via alpha 1-adrenergic receptors, which stimulate the release of nitric oxide (NO) from nitricoxidergic (NOergic) neurons in the medial basal hypothalamus (MBH). The NO activates guanylate cyclase and cyclooxygenase, thereby inducing release of LHRH into the hypophyseal portal vessels. We tested the hypothesis that these two catecholamines modulate NO release by local feedback. MBH explants were incubated in the presence of sodium nitroprusside (NP), a releaser of NO, and the effect on release of catecholamines was determined. NP inhibited release of norepinephrine. Basal release was increased by incubation of the tissue with the NO scavenger hemoglobin (20 micrograms/ml). Hemoglobin also blocked the inhibitory effect of NP. In the presence of high-potassium (40 mM) medium to depolarize cell membranes, norepinephrine release was increased by a factor of 3, and this was significantly inhibited by NP. Hemoglobin again produced a further increase in norepinephrine release and also blocked the action of NP. When constitutive NO synthase was inhibited by the competitive inhibitor NG-monomethyl-L-arginine (NMMA) at 300 microM, basal release of norepinephrine was increased, as was potassium-evoked release, and this was associated in the latter instance with a decrease in tissue concentration, presumably because synthesis did not keep up with the increased release in the presence of NMMA. The results were very similar with dopamine, except that reduction of potassium-evoked dopamine release by NP was not significant. However, the increase following incubation with hemoglobin was significant, and hemoglobin, when incubated with NP, caused a significant elevation in dopamine release above that with NP alone. In this case, NP increased tissue concentration of dopamine along with inhibiting release, suggesting that synthesis continued, thereby raising the tissue concentration in the face of diminished release. When the tissue was incubated with NP plus hemoglobin, which caused an increase in release above that obtained with NP alone, the tissue concentration decreased significantly compared with that in the absence of hemoglobin, indicating that, with increased release, release exceeded synthesis, causing a fall in tissue concentration. When NO synthase was blocked by NMMA, the release of dopamine, under either basal or potassium-evoked conditions, was increased. Again, in the latter instance the tissue concentration declined significantly, presumably because synthesis did not match release. Therefore, the results were very similar with both catecholamines and indicate that NO acts to suppress release of both amines. Since both catecholamines activate the release of LHRH, the inhibition of their release by NO serves as an ultra-short-loop negative feedback by which NO inhibits the release of the catecholamines, thereby reducing the activation of the NOergic neurons and decreasing the release of LHRH. This may be an important means for terminating the pulses of release of LHRH, which generate the pulsatile release of LH that stimulates gonadal function in both male and female mammals.

Animals↗

PubMed1995

Nitric oxide inhibits hypothalamic luteinizing hormone-releasing hormone release by releasing gamma-aminobutyric acid.

Nitric oxide synthase (NOS)-containing neurons, termed NOergic neurons, occur in various regions of the hypothalamus, including the median eminence-arcuate region, which plays an important role in controlling the release of luteinzing hormone-releasing hormone (LHRH). We examined the effect of NO on release of gamma-aminobutyric acid (GABA) from medial basal hypothalamic (MBH) explants incubated in vitro. Sodium nitroprusside (NP) (300 microM), a spontaneous releaser of NO, doubled the release of GABA. This release was significantly reduced by incubation of the tissue with hemoglobin, a scavenger of NO, whereas hemoglobin alone had no effect on the basal release of GABA. Elevation of the potassium concentration (40 mM) in the medium increased GABA release 15-fold; this release was further augmented by NP. Hemoglobin blocked the increase in GABA release induced by NP but had no effect on potassium-induced release, suggesting that the latter is not related to NO. As in the case of hemoglobin, NG-monomethyl-L-arginine (NMMA), a competitive inhibitor of NOS, had no effect on basal release of GABA, which indicates again that NO is not significant to basal GABA release. However, NMMA markedly inhibited the release of GABA induced by high potassium, which indicates that NO plays a role in potassium-induced release of GABA. In conditions in which the release of GABA was substantially augmented, there was a reduction in GABA tissue stores as well, suggesting that synthesis of GABA in these conditions did not keep up with release of the amine. Although NO released GABA, there was no effect of the released GABA on NO production, for incubation of MBH explants with GABA had no effect on NO release as measured by [14C]citrulline production. To determine whether GABA had any effect on the release of LHRH from these MBH explants, GABA was incubated with the tissue and the effect on LHRH release was determined. GABA (10(-5) or 10(-6) M) induced a 70% decrease in the release of LHRH, indicating that in the male rat GABA inhibits the release of this hypothalamic peptide. This inhibition in LHRH release induced by GABA was blocked by NMMA (300 microM), which indicates that GABA converts the stimulatory effect of NO on LHRH release into an inhibitory one, presumably via GABA receptors, which activate chloride channels that hyperpolarize the cell. Previous results have indicated that norepinephrine stimulates release of NO from the NOergic neurons, which then stimulates the release of LHRH. The current results indicate that the NO released also induces release of GABA, which then inhibits further LHRH release. Thus, in vivo the norepinephrinergic-driven pulses of LHRH release may be terminated by GABA released from GABAergic neurons via NO.

Animals↗

PubMed1995

Role of nitric oxide in control of prolactin release by the adenohypophysis.

Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 micrograms/ml) or NMMA and was completely blocked by 1 mM nitroarginine methyl ester. Atrial natriuretic factor at 1 microM also reduced prolactin release, and its action was completely blocked by NMMA. In contrast to these results with prolactin, luteinizing hormone (LH) was measured in the same medium in which the effect of nitroprusside was tested on prolactin release, there was no effect of nitroprusside, hemoglobin, or the combination of nitroprusside and hemoglobin on luteinizing hormone release. Therefore, in contrast to its inhibitory action on prolactin release NO had no effect on luteinizing hormone release. Immunocytochemical studies by others have shown that NO synthase is present in the folliculostellate cells and also the gonadotrophs of the pituitary gland. We conclude that NO produced by either of these cell types may diffuse to the lactotropes, where it can inhibit prolactin release. NO appears to play little role in the prolactin-releasing action of vasoactive intestinal polypeptide and substance P, but mediates the prolactin-inhibiting activity of dopamine and atrial natriuretic factor.

Amino Acid Oxidoreductases↗

PubMed1994

Involvement of hypothalamic substance P in the effect of prolactin on dopamine release.

In order to examine the role of hypothalamic SP in the feedback regulation of prolactin, we studied the effect of prolactin and dopamine on SP concentration and release, and the effect of SP on dopamine release. Hypothalamic fragments from male Wistar rats were incubated in the presence of prolactin, dopamine or SP under basal and K(+)-stimulated conditions. SP (10(-7) M) stimulated dopamine release, while dopamine (10(-7) M) decreased SP content and release. Prolactin (100 ng ml-1) increased SP content and release. An increase in hypothalamic SP content was also found during suckling. In addition, a specific antagonist for SP, Win 62,577, blocked the effect of prolactin and dopamine release. These results show an interaction between SP and dopamine at the hypothalamic level and suggest that SP could mediate the feedback action of prolactin on dopamine release.

Androstenes↗

PubMed1990

Ethanol-related changes in substance P in the hypothalamus and anterior pituitary.

The effect of the administration of a rabbit anti-substance P serum (ASPS) was studied in rats receiving an acute injection of ethanol. ASPS lowered serum prolactin levels and reduced the hyperprolactinemia induced by ethanol. ASPS also decreased LH serum levels in both saline- and ethanol-treated rats. The effect of ethanol on the concentration of substance P-like immunoreactivity (SP-LI) in the mediobasal hypothalamus and the anterior pituitary gland was also investigated. Ethanol reduced SP-LI in the mediobasal hypothalamus but increased it in the anterior pituitary gland. The presence of ethanol (50 mM) did not affect the K(+)-evoked release of SP-LI from either mediobasal hypothalamus or anterior pituitary gland, though it increased the SP-LI concentration remaining in this gland. These results indicate that ethanol increases the content of SP-LI in the anterior pituitary gland and suggest that substance P may be involved in the prolactin release induced by the acute administration of ethanol.

Animals↗

PubMed1990

Vasoactive intestinal peptide affects the GABAergic system in the hypothalamic-pituitary axis.

The effect of a specific antiserum against vasoactive intestinal peptide (VIP) on GABA in the hypothalamic-pituitary axis was studied. The administration of anti-VIP serum (A-VIP) increased anterior pituitary GABA concentration in control rats, but decreased this neurotransmitter in rats with hyperprolactinemia induced by acute or chronic treatments with estrogens, or by the implanting of anterior pituitary glands under the kidney capsule. Besides, the injection of the A-VIP serum in the morning in proestrous rats causes a decrease in anterior pituitary GABA concentration, measured in the afternoon of the same day. The in vitro effect of A-VIP and VIP on endogenous GABA release from hypothalamic fragments and on anterior pituitary GABA concentration was studied. A-VIP increased both basal and high K(+)-evoked GABA effluxes whereas VIP produced a decrease in evoked GABA efflux from hypothalamic fragments. Furthermore, A-VIP inhibited the normal degradation of GABA that occurs in the isolated gland whereas VIP increased it. These results suggest that VIP modifies hypothalamic GABA release and anterior pituitary GABA concentration.

Animals↗

PubMed1989

Estriol affects prolactin and LH secretion in rats.

The effects of estriol on serum prolactin (PRL) and LH levels, on the pituitary response to TRH and LHRH and on the synthesis and release of PRL from the anterior pituitary gland were investigated in female rats. The increase of serum PRL levels after estradiol administration was found to be associated with an increase of glutamic acid decarboxylase (GAD) and GABA-transaminase (GABA-T) in the hypothalamus. Thus, a study was carried out on the effects of estradiol and estriol on PRL secretion and on GAD, GABA-T and gamma-amino butyric acid (GABA) in the hypothalamus and the anterior pituitary. Under basal and TRH-stimulated conditions, estriol increased serum PRL levels, decreased basal serum LH levels, and increased the response to LHRH, in terms of LH release. Estradiol and estriol increased the synthesis and release of 3H-PRL from hemipituitary glands in incubations of pretreated animals. Both estrogens induced hyperprolactinemia, concomitantly with an increase of hypothalamic GAD and GABA-T activity. Estriol increased hypothalamic GABA concentration, but did not modify GABA concentration in the pituitary glands. Our results show that estriol, at relatively high doses, seems to be active in increasing PRL synthesis and release and in decreasing serum LH levels; it can also modify pituitary response to TRH and LHRH stimulation.

4-Aminobutyrate Transaminase↗

PubMed1988

Effect of sex steroids on GABA receptors in the rat hypothalamus and anterior pituitary gland.

Our data indicate that sex steroids modify the number of GABA receptors, as detected by a [3H]muscimol binding assay, in the tuberoinfundibular GABAergic system. GABA binding was affected by chronic hormonal treatments in different ways depending on the sex of the rats and the steroids administered. Estradiol increased GABA binding in ovariectomized female rats while testosterone decreased the number of GABA binding sites in gonadectomized male rats. These results suggest a sex difference in the regulation of hypothalamic GABA receptors.

Animals↗

PubMed1988

Effect of ethanol on GABA uptake and release from hypothalamic fragments.

A study was performed on the effect of ethanol on the basal and K+-evoked efflux of endogenous GABA from rat hypothalamic fragments. The amount of GABA present in the medium and in the tissue was measured by radioreceptor assay. In vitro addition of ethanol (50 and 100 mM) enhanced the K+-evoked efflux of GABA in a Ca++-dependent manner, and increased tissue GABA content. Since K+-evoked outflow induced by ethanol was not affected by the presence of nipecotic acid, ethanol appears to alter the uptake of endogenous GABA. An inhibitory effect of ethanol on 3H-GABA uptake was observed under K+ depolarization. On the other hand, acute ethanol administration produced a decrease in basal and K+-evoked efflux from hypothalamic fragments and in tissue GABA concentration. Changes in GABA efflux may lie behind some of the neuropharmacological effects of ethanol.

Animals↗

PubMed1988

Possible mechanisms of action of ethanol-induced release of prolactin from rat anterior pituitary.

We have demonstrated previously that ethanol increases the in vitro synthesis and release of prolactin by the anterior pituitary gland. In the present study we have examined the possible role of calcium and calmodulin in the ethanol-stimulation of in vitro prolactin release from hemipituitary glands. We also investigated the effect of inhibitors of arachidonic acid metabolism on the release of prolactin induced by ethanol. In addition we studied the effect of ethanol on the release of prostaglandins and the conversion of arachidonic acid to hydroperoxides. Basal and ethanol-stimulated prolactin release was almost blocked completely by omitting calcium from the incubation medium. In vitro addition of calmodulin-blocking agents such as pimozide and trifluoperazine reduced basal and ethanol-induced prolactin release. Acetylsalicylic acid, an inhibitor of the cycloxygenase pathway, had no effect on prolactin release. Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, blocked completely the release of prolactin induced by ethanol. Ethanol (5 and 10 mM) significantly increased the release of prostaglandin E2 and prostaglandin F2 alpha and the conversion of [14C]arachidonic acid to 5-hydroxyeicosatetraenoic acid. The results of this study show that ethanol increases prolactin release by a calcium-dependent mechanism. Besides, our data suggest that arachidonic acid metabolism is involved in ethanol-stimulated prolactin secretion and that lipoxygenase pathway metabolites are at least partially responsible for this effect.

Animals↗

PubMed1987

Effect of an anti-substance P serum on prolactin and gonadotropins in hyperprolactinemic rats.

The effects of the acute injection of a rabbit anti-substance P serum (ASPS) were studied in normal rats and rats with hyperprolactinemia induced by 5-hydroxytryptophan and estradiol given as a short or chronic treatment. The anti-substance P serum decreased the release of prolactin induced by 5-hydroxytryptophan when this serotonin precursor was injected 24 h, but not 1 h, after the administration of the antiserum. ASPS reduced the hyperprolactinemia induced by short and chronic treatment with estradiol in castrated rats. This effect was observed 24 h after the injection of the antiserum. On the other hand, the injection of ASPS induced a significant decrease in LH levels in serum of intact male rats injected with 5-hydroxytryptophan 24 h after ASPS, and in castrated rats treated with short-term and chronic administration of estradiol, 24 h after the injection of the antiserum. These results suggest that substance P may have a role in the control of prolactin secretion and could play a part in the hyperprolactinemic effects of estradiol. On the other hand, substance P, under certain circumstances, may stimulate LH release.

5-Hydroxytryptophan↗

PubMed1987

The effect of prolactin on glutamate decarboxylase activity and GABA concentration in hypothalamic slices.

The effect of prolactin on the activity of GABA-related enzymes and GABA concentrations were studied in hypothalamic slices incubated in vitro. After short periods of incubation (up to 40 min), prolactin (0.25 micrograms/ml) added to the incubation medium produced a significant increase (21% at 20 min of incubation) in glutamic acid decarboxylase (GAD) activity in the hypothalamic slices. A higher concentration of prolactin (1.0 micrograms/ml) produced a slight but significant decrease (8% at 20 min of incubation) in hypothalamic GAD activity. However, after longer periods of incubation (over 8 hr), both doses of prolactin induced a sustained increase in hypothalmic GAD activity, a response which depends upon protein synthesis. No changes were observed in GABA-transaminase (GABA-T) activity of hypothalamic slices incubated in the presence of prolactin. Prolactin decreased GABA concentration in the hypothalami incubated for 10 hr and, at the same time, increased GABA release into the medium. These results indicate that prolactin modifies the synthesis and release of hypothalmic GABA and suggest the existence of a feedback mechanism that prolactin may exert directly at the hypothalamic level.

Animals↗

PubMed1987

Mechanisms of endogenous GABA release from hypothalamic fragments. Effect of prolactin.

The efflux of endogenous gamma-aminobutyric acid (GABA) has been studied using small hypothalamic fragments containing arcuate-paraventricular nuclei and median eminence from the rat brain. The amount of GABA present in the medium and the tissue GABA content were quantified by radioreceptor assay. The endogenous GABA efflux was found to be dependent upon the Ca2+ and K+ concentrations in the incubation medium, and it required synthesis of GABA, indicating neuronal origin of the released neurotransmitter. Nipecotic acid, an inhibitor of neuronal and glial uptake, prevented reuptake of released GABA. Prolactin in concentrations of 250 and 1,000 ng/ml augmented the K+-evoked efflux of GABA. The effect of prolactin was dependent on the presence of Ca2+ and on the synthesis of GABA. In addition, prolactin seems to alter the reuptake of endogenous GABA and the uptake of [3H]-GABA. In conclusion, these results suggest that prolactin may influence its own secretion by stimulating the release of hypothalamic GABA, both through an increase of its synthesis and a modification of its reuptake.

3-Mercaptopropionic Acid↗