Effects of N-methyl-D-aspartic acid and kainic acid on prolactin secretion in hyper- and hypoprolactinaemic conditions

Pinilla, Leonor; Tena‐Sempere, Manuel; Aguilar, Rafaela; Aguilar, E.

doi:10.1530/eje.0.1380460

Cited by 8 publications

(6 citation statements)

References 30 publications

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“…In this experimental paradigm, AMPA was unable to decrease PRL secretion, suggesting that an increase in dopamine release might be involved in the inhibitory action of AMPA. These data are in line with results from experiments in male rats showing that pretreatment with -methyl-p-tyrosine (an inhibitor of DA biosynthesis) blocked the inhibitory effect of AMPA on PRL secretion (our unpublished results), and with our previous data showing that in prepubertal females activation of NMDA and KA receptors increased dopamine release, which in turn reduced prolactin secretion (Pinilla et al 1996b(Pinilla et al , 1998. However, it has to be considered that, in our experimental model, removal of dopaminergic regulation resulted in a dramatic increase in PRL secretion, and thus the possibility remains that activation of AMPA receptors resulted, in addition, in decreased secretion of PRFs such as vasointestinal peptide, thyrotropin-releasing hormone or the newly characterized PRL-releasing peptide (Kato et al 1978, Fagin & Neill 1981, Hinuma et al 1998.…”

Section: Discussionsupporting

confidence: 92%

Role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the control of prolactin, growth hormone and gonadotropin secretion in prepubertal rats

Gonzalez

Pinilla²,

Tena‐Sempere³

et al. 1999

Journal of Endocrinology

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Excitatory amino acids, such as glutamate, constitute a major transmitter system in the control of hypothalamicpituitary secretion. Different subtypes of glutamate receptors, such as NMDA (N-methyl--aspartic acid) and KA (kainate) receptors, are involved in the control of anterior pituitary secretion. Other receptor subtypes, such as AMPA (activated by -amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and metabotropic receptors, have been identified, although their role in the control of neuroendocrine function remains largely unknown. Recent reports have demonstrated the involvement of AMPA receptors in the control of the steroidinduced luteinizing hormone (LH) surge in female and growth hormone (GH) secretion in male rats. The aim of this study was to assess the potential role of AMPA receptors in the control of GH, prolactin (PRL), LH and follicle-stimulating hormone (FSH) secretion in prepubertal 23-day-old rats. To this end, prepubertal female rats were injected with AMPA (2·5 or 5 mg/kg i.p.) or the antagonist of AMPA receptors 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo (f ) quinoxaline-7-sulfonamide (NBQX; 0·25 or 0·50 mg/kg i.p.). Serum LH and FSH concentrations and hypothalamic LH-releasing hormone (LHRH) content remained unchanged after AMPA or NBQX administration. In contrast, serum PRL levels significantly decreased 15, 30 and 60 min after i.p. administration of AMPA and increased 120 min after NBQX treatment, whereas serum GH levels increased after AMPA treatment and decreased after NBQX administration. Considering that AMPA has been shown to activate a subset of kainate receptors, its effects were compared with those elicited by 2·5 mg/kg KA in prepubertal female rats. At this age, however, KA was unable to reproduce the effects of AMPA on PRL and GH secretion, thus suggesting that the actions observed after AMPA administration were carried out specifically through AMPA receptors. In addition, as the effects of AMPA on LH secretion in adult females have been proved to be steroid-dependent, the effects of AMPA (2·5 mg/kg) and NBQX (0·5 mg/kg) were tested in prepubertal animals with different gonadal backgrounds, i.e. intact males, and intact and ovariectomized (OVX) females. The effects of AMPA in prepubertal females appeared to be modulated by ovarian secretion, as the inhibition of PRL secretion disappeared and LH secretion was partially suppressed by AMPA in OVX animals whereas the stimulatory effect on GH release was enhanced by ovariectomy. Furthermore, in male rats, AMPA administration significantly decreased PRL secretion and increased serum GH levels, the amplitude of the GH response being higher than in prepubertal females. To ascertain the pituitary component for the reported actions of AMPA, hemi-pituitaries of male rats were incubated in the presence of AMPA (10 8 -10 6 M). The results obtained showed no effect of AMPA on PRL, GH and gonadotropin secretion in vitro. Finally, we investigated the involvement of the dopaminergic (DA) system in the inhibitory action of AMPA on PR...

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Section: Discussionsupporting

confidence: 92%

Role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the control of prolactin, growth hormone and gonadotropin secretion in prepubertal rats

Gonzalez

Pinilla²,

Tena‐Sempere³

et al. 1999

Journal of Endocrinology

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“…The available data indicate that ghrelin action is exerted via mechanisms different from those used by EAAs, since: (a) the inhibitory action of NMDA, KA and AMPA upon PRL secretion appeared to be dependent on an increase in DA release [19, 20, 21, 22, 23, 24, 25, 31], and (b) ghrelin significantly inhibited PRL-stimulated secretion by elevation of the serotoninergic tone (with fluoxetine + 5-HTP), whereas AMPA was ineffective in this experimental model [32]. Despite the possibility of different mechanisms of action for the effects of ghrelin and EAAs, in our experiments, the effects of ghrelin and the agonists of ionotropic EAA receptors NMDA and AMPA were not additive, which suggests that each compound, at the doses used, maximally inhibited the PRL secretion and no further decreases can be induced by simultaneous administration of agonists of ghrelin and ionotropic EAA receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Experiment 6: We have previously described that in prepubertal rats, activation of NMDA, KA or AMPA receptors decreases PRL secretion [21, 22, 23, 24, 25, 26, 27, 32]. To analyze the possible interactions between the inhibitory effects of EAAs (through NMDA and AMPA receptors) and ghrelin on PRL secretion, 23-day-old male rats were i.p.…”

Section: Methodsmentioning

confidence: 99%

Ghrelin Inhibits Prolactin Secretion in Prepubertal Rats

et al. 2004

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Ghrelin, a novel 28-amino-acid peptide primarily expressed in stomach and hypothalamus, has recently emerged as the endogenous ligand for the GH-secretagogue receptor with ability to stimulate GH secretion in humans and rats. In addition, ghrelin also stimulates prolactin (PRL) secretion in humans. However, its role in the regulation of PRL secretion in rats remains largely unknown. In this context, the present experiments were carried out to analyze the effects of ghrelin on PRL secretion in male and female rats. In detail, the ontogeny and potential sexual dimorphism in the PRL response to ghrelin was evaluated. In addition, the hypothalamic and/or pituitary site of primary action of ghrelin, as well as the possible interactions between ghrelin and other neurotransmitters, as nitric oxide, dopamine, serotonin or excitatory amino acids, in the precise control of PRL secretion were assessed. Experiments were conducted in prepubertal male and female animals. Systemic (i.p.) and central (i.c.v.) administration of ghrelin significantly inhibited PRL secretion. Such an inhibitory effect became evident after day 10 of age, was similar in males and females, and was also observed in hyperprolactinemic aged female rats. In contrast, however, challenge of pituitary samples in vitro with increasing doses of ghrelin (10^–9–10^–7M) failed to inhibit PRL secretion. Analysis of interactions between ghrelin and other systems involved in the control of PRL secretion revealed that neither blockade of dopaminergic receptors with domperidone, nor enhancement of serotoninergic tone with fluoxetine + 5-hydroxytryptophan altered the inhibitory response to ghrelin in terms of PRL secretion. Similarly, blockade of nitric oxide synthases with L-nitro-arginine-methyl ester failed to modify the magnitude of ghrelin-induced inhibition of PRL secretion, whereas ghrelin was unable to further decrease serum PRL levels after activation of ionotropic excitatory amino acid receptors by administration of NMDA or AMPA. In conclusion, our data indicate that ghrelin is able to inhibit PRL secretion in male and female rats, likely through an extrapituitary primary site of action that is independent of nitric oxide, dopamine, and serotonin systems.

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“…It has been proposed that the effects of glutamate agonists on PRL secretion depend on the previous circulating concentrations of the hormone, with a conversion of the PRL response from stimulation when basal secretion is low to an inhibitory effect in hyperprolactinaemic situations (Abbud & Smith 1991). However, previous data from our laboratory indicated that, at least partially, the dual effect of NMDA on PRL secretion is independent of prior PRL concentrations (Pinilla et al 1998).…”

Section: Introductionmentioning

confidence: 85%

“…Thereafter, the drugs were dissolved in saline up to the working concentration. The doses and route of administration of different drugs as well as the time-points for hormone measurements were selected based on the previously reported effectiveness (Negro-Vilar et al 1979, Martin et al 1995, Pinilla et al 1998, Gonzalez et al 1999a and the absence of behavioural changes. In addition, to analyse the effectiveness of AMPA to change PRL secretion after blockade of different receptor subtypes as well and in hyper-and hypo-prolactinaemic situations, NBQX, MK-801, -MPT, DDC, 5-HTP and fluoxetine were injected prior to AMPA administration.…”

Section: Animals and Drugsmentioning

confidence: 99%

Regulation of prolactin secretion by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in male rats

Gonzalez

Pinilla²,

Tena‐Sempere

et al. 2000

Journal of Endocrinology

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The secretion of PRL is controlled by different hypothalamic signals. Depending on the experimental model, PRL secretion increases or decreases after activation of N-methyl--aspartic acid and kainate receptors. Recently we have described that activation of -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors inhibits PRL secretion in prepubertal male rats. The aim of present study was to examine (1) the physiological relevance of this finding, (2) the possible age-related changes observed after activation or blockade of AMPA receptors, (3) the specificity of the AMPA effect, (4) the hypothalamic and/or pituitary localization of AMPA action, and (5) the mechanism(s) of action of AMPA agonists.In a first set of experiments, neonatal males (5 and 10 days old) and prepubertal (23 days old) male rats were injected with AMPA (1, 2·5 or 5 mg/kg) or the antagonist of AMPA receptors 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo (f) quinoxaline-7-sulfonamide (NBQX; 0·25 or 0·50 mg/kg). Serum PRL concentrations decreased significantly 15 and 30 min after i.p. administration of AMPA in prepubertal male rats, while the inhibitory effect of AMPA was not observed in 5-and 10-day-old males. The effect of AMPA was abolished by NBQX but not by MK-801 (a selective antagonist of NMDA receptors). NBQX alone (0·25 or 0·50 mg/kg) had no effect on PRL release. In vitro, AMPA slightly stimulated PRL secretion by hemipituitaries from prepubertal males, suggesting that the hypothalamus is likely the site of action for the reported inhibitory action of AMPA on PRL release. In this sense, the blockade of AMPA effects in animals pretreated with domperidone (a dopaminergic antagonist) or -methyl-p-tyrosine (an inhibitor of dopamine synthesis) suggests that an increase in the release of hypothalamic dopamine is probably the mechanism involved in the effect of AMPA. In a second set of experiments, the effects of AMPA (2·5 mg/kg i.p.) and NBQX (0·5 mg/kg i.p. and 20 or 40 nmol i.c.v.) were tested in freely moving adult male rats sampled during periods of 2, 3 or 6 h. In contrast with data obtained in prepubertal rats, neither AMPA nor NBQX affected PRL secretion.In conclusion, these data indicate that activation of AMPA receptors inhibits PRL secretion in prepubertal male rats. This effect probably involves the release of dopamine from the hypothalamus and disappears in adulthood.

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Effects of N-methyl-D-aspartic acid and kainic acid on prolactin secretion in hyper- and hypoprolactinaemic conditions

Cited by 8 publications

References 30 publications

Role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the control of prolactin, growth hormone and gonadotropin secretion in prepubertal rats

Role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the control of prolactin, growth hormone and gonadotropin secretion in prepubertal rats

Ghrelin Inhibits Prolactin Secretion in Prepubertal Rats

Regulation of prolactin secretion by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in male rats

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