Inhibition of Stress-Induced Adrenocorticotropin and Prolactin Secretion Mediating Hypophysiotropic Factors by Antagonist of AMPA Type Glutamate Receptor

Abstract

Abstract. Glutamate is the dominant excitatory neurotransmitter in a large number of physiological processes including neuroendocrine regulation. Some pharmacological studies have shown that different subtypes of glutamate receptor, such as the N-methyl-D-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methy-4-isoxazolepropionic acid (AMPA) receptors, are involved in stress-induced adrenocorticotropin (ACTH) and prolactin secretion. However, the roles of the respective glutamate receptors and the mechanism of ACTH and prolactin secretion during stress via these receptors have not been investigated in detail. In the present study, we evaluated the role of AMPA-type glutamate receptor in ACTH and prolactin regulation under restraint stress in adult male rats. Male rats pretreated with a selective AMPA receptor antagonist, 2, 3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX; 50 µg), through a lateral ventricle cannula were stressed by immobilization. Administration of NBQX inhibited ACTH and prolactin secretion in response to restraint stress. However, NBQX had no significant effects on the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis, as measured by the accumulation of 3, 4-dihydroxyphenylalanine (DOPA). In addition, administration of NBQX suppressed stress-induced prolactin secretion in the male rats pretreated with α-MT, an inhibitor of dopamine synthesis, and infused with dopamine solution (2.5 µg/200 µl/10 min). These results indicated that the effects of NBQX on prolactin secretion might be mediated by non-dopamine mechanisms. The contents of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the median eminence (ME) of the male rats decreased during restraint stress; however, the fluctuations in CRH and AVP were eliminated by NBQX administration. These results suggest that stress-induced ACTH and prolactin release mediated by neurotransmission via AMPA receptors might be partly attributable to hypophysiotropic regulatory factors in the hypothalamus. Key words: Adrenocorticotropin (ACTH), α-Amino-3-hydroxy-5-methy-4-isoxazolepropionic acid (AMPA), Prolactin, Rat, Stress (J. Reprod. Dev. 53: [545][546][547][548][549][550][551][552][553][554] 2007) he excitatory amino acid glutamate is the primary mediator of excitatory synaptic transmission in the central nervous system [1,2].

Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men

“…Contrary to our hypothesis, there was even a weak indication of increased growth hormone secretion during the hypoglycaemic plateau. In rats, intracerebral stimulation of AMPA receptors induces elevations of plasma ACTH [6] and their antagonisation inhibits ACTH and prolactin secretion in response to immobilisation stress [7]. At first glance, these results conflict with our observations of unchanged HPA axis activity.…”

“…Differences in the administration route between animal and human studies may also be crucial for the effects of glutamatergic interventions. In our experiments, caroverine was administered intravenously, whereas most animal studies used the intracerebroventricular or intracerebral route [6,7]. It is conceivable that peripherally administered caroverine does not reach the hypothalamus in sufficient quantities or, additionally, that AMPA receptor antagonism in other brain areas counteracts the hypothalamic effects of caroverine on neuroendocrine systems.…”

“…As the glutamate signal is conveyed by amino-3-hydroxy-5-methyl-4-isoxazol propionate (AMPA) receptor subtypes, whereas NMDA receptors are thought to play a role in inducing or modulating the plasticity of AMPA receptor-mediated transmission, the above finding raises the question as to what role AMPA receptors play in the acute neuroendocrine and neurocognitive response to hypoglycaemia in humans. In rats, pharmacological blockade of AMPA receptors diminished the neuroendocrine response to immobilisation stress [5][6][7]. Against this background, we assessed neuroglycopenic and autonomic symptoms, and neuroendocrine responses to insulin-induced hypoglycaemia in healthy men after pretreatment with the AMPA receptor antagonist caroverine.…”

Pre-emptive oral dexmethorphan reduces fentanyl-induced cough as well as immediate postoperative adrenocortico-tropic hormone and growth hormone level

“…Glutamate is believed to interact with NMDA and non-NMDA receptors. [23] Studies on NMDA receptors included a variety of NMDA receptor antagonists and which monitored their effects on stress hormones release. It is believed that ACTH is a sensitive marker to detect the severity of surgical trauma and the associated stress response.…”