Swenson K L, Badre S E, Morsette D J, Sladek C D
Department of Physiology and Biophysics, Finch University of Health Sciences, The Chicago Medical School, North Chicago, IL 60064, USA.
J Neuroendocrinol. 1998 Sep;10(9):679-85. doi: 10.1046/j.1365-2826.1998.00257.x.
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.
先前的实验表明，兴奋性氨基酸参与血管加压素分泌的渗透调节，但N-甲基-D-天冬氨酸（NMDA）受体的具体参与情况未作评估。本研究证实了这一点。NMDA刺激下丘脑-神经垂体系统（HNS）灌流外植体释放血管加压素，而NMDA受体拮抗剂MK-801（10微摩尔）和AP5（100微摩尔）可抑制血管加压素释放的渗透刺激。NMDA的有效浓度取决于灌流液中的Mg2+浓度，在Mg2+充足时1微摩尔NMDA可观察到刺激作用，而在低Mg2+培养基中则为5微摩尔。先前的实验还表明，雌二醇和双氢睾酮（DHT）抑制渗透刺激的血管加压素分泌，与牛血清白蛋白结合的类固醇能够复制这种效应，提示其作用机制为非基因组机制。进行实验以探讨NMDA受体在该机制中的潜在作用。雌二醇（50皮克/毫升）和DHT（3纳克/毫升）抑制灌流HNS外植体中NMDA刺激的血管加压素释放。这些结果表明NMDA受体在渗透刺激释放中血管加压素分泌的介导过程中发挥作用。此外，雌二醇和DHT可能通过NMDA受体对渗透刺激的血管加压素释放发挥抑制作用。
