N-METHYL-D-ASPARTIC ACID STIMULATION OF VASOPRESSIN RELEASE - ROLE INOSMOTIC REGULATION AND MODULATION BY GONADAL-STEROIDS

Previous experiments demonstrated that excitatory amino acids particip ate in the osmotic regulation of vasopressin secretion, but the specif ic involvement of N-methyl-D-aspartic acid (NMDA) receptors was not ev aluated. This was demonstrated in the present studies. NMDA stimulated vasopressin release from perifused explants of the hypothalamo-neuroh ypophyseal system (HNS), and osmotic stimulation of vasopressin releas e was inhibited by MK-801 (10 mu M) and AP5 (100 mu M) NMDA receptor a ntagonists. The effective concentration of NMDA was dependent upon the Mg2+ concentration of the perifusate with stimulation observed at 1 m u M NMDA in Mg2+-replete compared with 5 mu M in low-Mg2+ medium. Prev ious experiments also demonstrated that estradiol and dihydrotestoster one (DHT) inhibited osmotically stimulated vasopressin secretion, and a nongenomic mechanism of action was suggested by the ability of stero ids conjugated to bovine serum albumin to replicate the effect. Experi ments were performed to explore the potential role of NMDA receptors i n this mechanism. Estradiol (50 pg/ml) and DHT (3 ng/ml) inhibited NMD A stimulated vasopressin release in perifused HNS explants. These resu lts suggest a role of NMDA receptors in the mediation of vasopressin s ecretion in osmotically stimulated release. Furthermore, estradiol and DHT may exert their inhibitory effect on osmotically stimulated vasop ressin release via the NMDA receptor.