N-methyl-D-aspartic acid stimulation of vasopressin release: role in osmotic regulation and modulation by gonadal steroids.
Previous experiments demonstrated that excitatory amino acids participate in the osmotic regulation of vasopressin secretion, but the specific involvement of N-methyl-D-aspartic acid (NMDA) receptors was not evaluated. This was demonstrated in the present studies. NMDA stimulated vasopressin release from perifused explants of the hypothalamo-neurohypophyseal system (HNS), and osmotic stimulation of vasopressin release was inhibited by MK-801 (10 microM) and AP5 (100 microM) NMDA receptor antagonists. The effective concentration of NMDA was dependent upon the Mg2+ concentration of the perifusate with stimulation observed at 1 microM NMDA in Mg2+-replete compared with 5 microM in low-Mg2+ medium. Previous experiments also demonstrated that estradiol and dihydrotestosterone (DHT) inhibited osmotically stimulated vasopressin secretion, and a nongenomic mechanism of action was suggested by the ability of steroids conjugated to bovine serum albumin to replicate the effect. Experiments were performed to explore the potential role of NMDA receptors in this mechanism. Estradiol (50 pg/ml) and DHT (3 ng/ml) inhibited NMDA stimulated vasopressin release in perifused HNS explants. These results suggest a role of NMDA receptors in the mediation of vasopressin secretion in osmotically stimulated release. Furthermore, estradiol and DHT may exert their inhibitory effect on osmotically stimulated vasopressin release via the NMDA receptor.
Swenson
K L
KL
Department of Physiology and Biophysics, Finch University of Health Sciences, The Chicago Medical School, North Chicago, IL 60064, USA.
Badre
S E
SE
Morsette
D J
DJ
Sladek
C D
CD
D000818:Animals; D013196:Dihydrotestosterone / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D013196:Dihydrotestosterone; D014667:Vasopressins; D004958:Estradiol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D008274:Magnesium