Studies of the role of the N-methyl-D-aspartate (NMDA) receptor in the hypothalamic control of prolactin secretion.
To further examine the role of excitatory amino acids in the control of prolactin (PRL) secretion, the effects of administering a specific agonist and an antagonist of the N-methyl-D-aspartate (NMDA) receptor on plasma PRL concentrations were examined in the adult male rat. Animals of the Sprague-Dawley strain weighing 250-300 g were implanted with an indwelling cardiac catheter via the right jugular vein. Blood samples were collected through the catheter at 5 min intervals for 40 min, beginning 5 min before the iv administration of drug or the saline vehicle (V). Plasma PRL and luteinizing hormone (LH) concentrations were estimated using RIAs. Groups of animals (n = 5-7) received N-methyl-D,L-aspartate (NMA), D,L-2-amino-5-phosphonopentanoic acid (AP5), AP5 and NMA, norvaline (NOR), or V. The effects of administering the NMDA receptor antagonist alone were studied on two separate occasions. Injection of NMA (4.5 mg/rat) resulted in unambiguous PRL and LH discharges. Treatment with AP5 (9 mg/rat) 1 min prior to NMA administration completely blocked the LH releasing action of NMA, but did not significantly alter the discharge of PRL. Injection of AP5, alone, generally elicited a distinct and robust discharge of PRL, although plasma LH levels in these animals remained unchanged. NOR, an amino acid structurally related to AP5, administered at a dose (5.3 mg/animal) isomolar to that of AP5, was without effect on PRL and LH secretion, as was injection of V alone. These findings suggest that neuroexcitatory amino acids acting at the NMDA receptor may play a role in modulating the activity of neuronal systems that govern the release of both PRL releasing factor (PRF) and PRL inhibiting factor (PIF) into hypophysial portal blood.
Arslan
M
M
Department of Physiology, University of Pittsburgh School of Medicine, PA 15261.
Pohl
C R
CR
Smith
M S
MS
Plant
T M
TM
D000818:Animals; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; D011388:Prolactin; C005313:norvaline; D014633:Valine