GLUTAMATE RECEPTORS OF THE NON-NORMAL-METHYL-D-ASPARTIC ACID TYPE MEDIATE THE INCREASE IN LUTEINIZING-HORMONE-RELEASING HORMONE-RELEASE BY EXCITATORY AMINO-ACIDS INVITRO

The present study was designed to analyze in detail the effects of L-glutamate (L-G1U) and its agonists on the release of LHRH from arcuate nucleus-median eminence (AN- ME) fragments in vitro. Fragments from adult male rats were incubated in Krebs-Ringer bicarbonate buffer in the presence of different concentrations of L-Glu, kainate (KA), N-methyl-D- aspartic acid (NMDA), and quisqualate (QA). L-G1U at 10-20 mM evoked a significant increase in basal LHRH release, while D-glutamate at similar concentrations was ineffective. Partial depolarization with 14 mM K+ significantly augmented the re-lease of LHRH induced by L-G1U. L-Glu-induced LHRH release was blunted in a dose-related manner by the specific KA/QA receptor antagonist 6, 7-dinitroquinoxaline-2, 3-dione. Exposure to KA or QA significantly increased LHRH release at concen-trations (1 mM) much lower than those required for L-Glu. In the presence of 14 mM K+ the potencies of KA and QA (0.075 and 0.1 mM, respectively) were significantly enhanced. 6, 7-Din- itroquinoxaline-2, 3-dione blocked KA-induced LHRH release, while AP-7, a competitive NMDA receptor antagonist, was inactive in preventing L-G1u- and KA-induced LHRH release. LHRH secretion from AN-ME fragments was unaffected by NMDA at concentrations up to 10 mM in the different media tested. A significant stimulatory effect of NMDA at 20 mM was observed when fragments were incubated in Mg2+-free medium. These results show the stereoselectivity of L-Glu to enhance LHRH release from AN-ME fragments in vitro. Moreover, in view of the respective potencies of excitatory amino acid agonists (KA = QA > L-G1u > NMDA) and the selective antagonism of excitatory amino acid effects, they provide evidence that non- NMDA receptors primarily mediate the excitatory actions of L- Glu on LHRH release from nerve terminals in the AN-ME. © 1990 by The Endocrine Society.