Glutamate receptors of the non-N-methyl-D-aspartic acid type mediate the increase in luteinizing hormone-releasing hormone release by excitatory amino acids in vitro.
The present study was designed to analyze in detail the effects of L-glutamate (L-Glu) 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-Glu 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 release of LHRH induced by L-Glu. 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 concentrations (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-Dinitroquinoxaline-2,3-dione blocked KA-induced LHRH release, while AP-7, a competitive NMDA receptor antagonist, was inactive in preventing L-Glu- 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 greater than L-Glu greater than 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.
Donoso
A O
AO
Reproductive Neuroendocrinology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
López
F J
FJ
Negro-Vilar
A
A
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D016202:N-Methylaspartate; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000502:physiology*
D000596:Amino Acids; D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D007987:Gonadotropin-Releasing Hormone; D016202:N-Methylaspartate