DL-2-amino-5-phosphonopentanoic acid, a specific N-methyl-D-aspartic acid receptor antagonist, suppresses pulsatile LH release in the rat.
To determine whether neuroexcitatory amino acids may play a role in generating intermittent hypothalamic GnRH release, the effect of N-methyl-D-aspartate (NMDA) receptor blockade on pulsatile LH secretion was examined in male rats. The ability of the NMDA receptor antagonist, DL-2-amino-5-phosphonopentanoic acid (AP5), to inhibit activation of the hypothalamic-pituitary gonadotroph axis that follows peripheral administration of NMDA, was first established in intact rats. Subsequently, acutely castrated rats (n = 12) bearing venous catheters received four consecutive intravenous injections of AP5 (3.75 mg/injection/rat; approx. 13.6 mg/kg BW/injection) at 15-min intervals. Blood samples were collected at 10-min intervals for 1 h before and 2 h after initiation of AP5 treatment, and plasma LH concentrations were determined by RIA. For control purposes, norvaline, and amino acid structurally related to AP5, was administered to a second group of animals (n = 7) in a quantity (2.25 mg/injection/rat; approx. 8.2 mg/kg BW/injection) equimolar to that of the NMDA receptor antagonist. A third group of animals (n = 8) received only saline, the vehicle employed to inject AP5 and norvaline. AP5, but not norvaline, resulted in a marked suppression of pulsatile LH secretion. These findings suggest that neuroexcitatory amino acids acting at the NMDA receptor may play a physiological role in generating the intermittent mode of hypothalamic GnRH release.
Arslan
M
M
Department of Physiology, University of Pittsburgh School of Medicine, Pa.
Pohl
C R
CR
Plant
T M
TM
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate; D009919:Orchiectomy; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; D007986:Luteinizing Hormone; D014633:Valine