Stimulation of oxytocin release in the lactating rat by central excitatory amino acid mechanisms: evidence for specific involvement of R,S-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-sensitive glutamate receptors.
To examine whether an excitatory amino acid (EAA) neurotransmitter may influence the secretion of oxytocin (OT), agonists and antagonists selective for three major groups of EAA receptors were microinjected into the area of right supraoptic nucleus (SON) of conscious unrestrained lactating rats. An increase in plasma OT concentration was induced by the EAA receptor agonist R,S-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainic acid, but not by agonists at other EAA receptors, such as N-methyl-D-aspartic acid (NMDA) or the metabotropic agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid. Increasing AMPA doses between 0.1-0.8 nmol/SON progressively increased the percentage of animals showing OT discharges to 100% at the highest dose, whereas the responding animals showed similar elevations of plasma OT regardless of dose. OT release induced by intra-SON AMPA was prevented by treatment with the selective non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, but not by antagonists of the NMDA receptor. Administration of this antagonist in the third ventricle blocked the release of OT and PRL induced by suckling. The L-type Ca2+ channel antagonist nimodipine and the Na+ channel inhibitor 3-amino-N-(aminoiminomethyl)5-(N-ethyl-N-isopropyl)6-chloropyra zinecarboxamide produced an additive blockade of AMPA-induced OT release, whereas the N-type Ca2+ channel-preferring antagonist omega-conotoxin GVIA had no effect. These findings suggest that an EAA, most likely glutamate, participates in the physiological regulation of OT release in the lactating rat via actions at an AMPA/kainate receptor subtype that gates Na+ and Ca2+.
Parker
S L
SL
Department of Pharmacology, University of Tennessee-Memphis College of Medicine, Memphis 38163.
Crowley
W R
WR
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D007774:Lactation / Q000097:blood*; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000097:blood*; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000097:blood; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers; D014667:Vasopressins / Q000097:blood; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D000596:Amino Acids; D002121:Calcium Channel Blockers; D011810:Quinoxalines; D017470:Receptors, Glutamate; D026941:Sodium Channel Blockers; D014667:Vasopressins; D010121:Oxytocin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011388:Prolactin