Glutamate Peripherally Administered Exerts Somatostatin‐Releasing Action in the Conscious Rat

Abstract

This study was designed to determine whether glutamate is able to stimulate somatostatin release from in vivo conscious animals when somatostatin release is monitored in unanaesthetized rats stereotaxically implanted with a push-pull cannula in the median eminence. One week after implantation, the median eminence was perfused with artificial cerebrospinal fluid alone or with the addition of either CGS 19755, an N-methyl-D-aspartate (NMDA) receptor antagonist M). The latter (which is able to cross the brain-blood barrier at large doses) was also peripherally administered (1 g/kg ip). Median eminence perfusate samples were collected every 15 min and somatostatin was measured by a sensitive radioimmunoassay. In rats receiving ip glutamate injection, somatostatin release from the median eminence was significantly increased (73.3+ 10.4 versus 24.8k6.2; P<O.Ol; n=5) when compared to baseline levels measured in the same animals, but no effect was observed when local perfusion of the median eminence with glutamate to M; n=6) was performed. Glutamate-induced somatostatin release was completely blunted (n = 5) by prior local administration of CGS 19755 M). a potent NMDA-type receptor antagonist able to cross the blood-brain barrier. In contrast, administration of glutamic acid diethylester, a competitive antagonist of non-NMDA receptors, at doses of M (n=4), was not able to alter this response.Our results are the first in vivo evidence in favour of a neuroendocrine role for glutamate on somatostatin release whose site M), or glutamate of action seems to exclude the median eminence.It is well established thit glutamic acid (GLU) acts as an excitatory neurotransmitter in several areas of the CNS (review in 1). A neuroendocrine action, similar to that of other neurotransmitters, is presumed from anatomical and pharmacological evidence. Decrease of GLU in the mediobasal hypothalamus (MBH) after deafferentation suggests the existence of fibres projecting from other portions of the hypothalamus and impinging on cells present in the MBH (2). On the other hand, systemic administration of GLU to adult rats causes an immediate longlasting suppression of growth hormone secretion presumably via somatostatin (SRIF) release as estimated by decrease in its hypothalamic content (3). Most convincing evidence of this neuroendocrine role arises from our recent data showing that in primary culture of hypothalamic neurons, GLU exerts a stimulatory action on SRIF release involving N-methyl-D-aspartate (NMDA) receptor subtypes (4). The present work was designed to determine whether this GLU-SRIF neuroendocrine interaction also operates in the in vivo adult rat.We thus peripherally administered GLU to conscious male rats and samples of hypothalamic perfusate were sequentially collected using push-pull perfusion ( 5 , 6 ) of the median eminence (ME) in order to assess SRIF release. ResultsIntraperitoneal (ip) injection of GLU (1 g/kg) significantly increased SRIF release compared to baseline levels measured in the same animal (73.3+ 10.4 ...

Testosterone modulates growth hormone secretion at the hypothalamic but not at the hypophyseal level in the adult male rhesus monkey

“…Finally, compared with that in normal boys, the GHRH response to -dopa stimulation is less in naturally androgen-deficient individuals with idiopathic delayed puberty (Argente et al 1987, Liapi et al 1988, whereas administration of oxandrolone to these patients significantly increases the -dopa induced GHRH release (Liapi et al 1988). NMA has previously been reported to stimulate the release of somatostatin in the median eminence in vivo (Benyassi et al 1991) and from cultured hypothalamic neurones in vitro (Rage et al 1993). Furthermore, NMDA induces a significant increase in somatostatin mRNA levels and the noncompetitive NMDA antagonist MK 801 has been shown to reduce somatostatin mRNA content significantly in cultured hypothalamic neurones in vitro (Rage et al 1994).…”

Regulation of brain‐derived neurotrophic factor transcripts by neuronal activation in rat hypothalamic neurons

“…These different regulations could be explained either by a differential expression of glutamate receptors in different cellular populations presenting only some promoters or by different glutamate receptors involved in the regulation of BDNF promoters. Indeed, previous studies have demonstrated the critical role played by glutamate through NMDA (Tapia‐Arancibia et Astier, 1988; Benyassi et al, 1991; Gu et al, 1999) and non‐NMDA ionotropic (van den Pol et al, 1990) or metabotropic receptors in the hypothalamus, both in the developing and in the adult brain (van den Pol et al, 1994, 1995; Ghosh et al, 1997). Moreover, a developmentally regulated expression of NMDA (Rage et al, 1994) or metabotropic glutamate receptors in the hypthalamus has been reported (Ghosh et al, 1997).…”

Effect of a Single Intravenous Injection of N‐Methyl‐D,L‐Aspartic Acid on Secretion of Luteinizing Hormone and Growth Hormone in Holstein Bull Calves

“…That NMA may not affect GHRH neurons directly could be inferred from a recent observation (25) that some excitatory actions of NMA are mediated by norepinephrine, which has previously been shown to be a GHRH secretagogue in rats (28). On the other hand, NMDA receptor activation has also been shown to lead to an increase in somatostatin release in the median eminence (29) and from hypothalamic neurons in vitro (30,31). It may therefore, be possible, as has been proposed for NMDAregulated PRL secretion (21,32) that NMDA receptor mediated neurotransmission alters both the GHRH and somatostatin rclease and the net GH secretion depends on the ratio of existing NMDA drives to the GHRH/somatostatin neurons.…”