Excitatory amino acids constitute a novel class of neurotransmitters, glutamate and aspartate being the most representative transmitters of the family. These substances can also induce extensive neuronal injuries, and can therefore act as excitotoxins. In addition to the toxic effects of these agents, they also exist in physiological conditions in the nervous system and, therefore, may contribute to the control of physiological events. Studies were designed to evaluate the actions and relative potency of different endogenous and excitatory amino acid (EAA) selective analogs on EAA-induced neuropeptide secretion as well as to analyze the receptor subtypes Involved. For this purpose, different glutamate agonists were tested for their ability to evoke release of the hypothalamic neuropeptide, luteinizing hormone-releasing hormone (LHRH), from arcuate nucleusmedian eminence fragments incubated in vitro. Different glutamate agonists, i.e., AMPA, kainic (KA), quisqualic -MAT,-homocysteic (HCA), quinolinic (QUIN), N-methyl-D-aspartic (NMDA) and pyroglutamic (PYR) acids, elicited LHRH release from AN-ME fragments in vitro. The observed rank of activities: AMPA>HCA>QUIN>PYR, suggests that non-NMDA receptors are primarily involved in EAA's-induced LHRH release at the level of the AN-ME. Evaluation of the receptor types involved using two specific antagonists for NMDA and non-NMDA receptors, AP-7 and CNQX, respectively showed that AMPA- and H.V',A-effects on LHRH release can be completely blocked by CNQX, whereas QUIN activity is blocked by AP-7. The effects of PYR on LHRH release were abolished by both receptor blockers. A metabotropic receptor agonist was not active in eliciting LHRH secretion. The data indicates that homocysteic, quinolinic and pyroglutamic acids, endogenous substances active at EAA receptor sites, can significantly increase secretion of the neuropeptide LHRH from nerve terminals and, thus, may participate in the physiological regulation of the activity of this Important

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES090058-03
Application #
3855996
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code