Effects of excitatory amino acid transmitters on hypothalamic corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) release in vitro: implications in pituitary-adrenal regulation.

The effect of excitatory amino acid (EAA) on the release of CRH and AVP--two major neurohumoral activators of the hypothalamic-pituitary-adrenal axis--was studied by in vitro perifusion of hypothalamic organ explants with various concentrations of EAA receptor agonists and antagonists. The agonists L-glutamate (GLU), kainic acid (KAIN) and L-aspartate (ASP) significantly decreased CRH release, while N-methyl-D-aspartate (NMDA) and quisqualic acid (QUIS) did not affect this parameter. AVP release was significantly stimulated by ASP and NMDA, decreased by KAIN and QUIS, and not influenced by GLU. Co-perifusion with equimolar concentrations of ASP and the selective NMDA receptor antagonist D-alpha-aminoadipic acid (aAA) partially diminished the effect of ASP on AVP release, but failed to affect ASP-induced suppression of CRH secretion. The broad-spectrum EAA receptor antagonist kynurenic acid (KYN) completely abolished ASP effects on CRH and AVP release in vitro. The results suggest that EAA transmitters might participate in the regulation of hypothalamic-pituitary-adrenal axis by differentially affecting the release of the two major ACTH secretagogues. In addition, EAA effects on hypothalamic CRH and AVP secretion appear to employ more than one subtype of amino acid receptors.