Morsette D J, Sidorowicz H, Sladek C D
Department of Physiology and Biophysics, Finch University of Health Sciences, The Chicago Medical School, North Chicago, Illinois 60064, USA.
Am J Physiol Regul Integr Comp Physiol. 2001 Feb;280(2):R313-22. doi: 10.1152/ajpregu.2001.280.2.R313.
Glutamate is recognized as a prominent excitatory transmitter in the supraoptic nucleus (SON) and is involved in transmission of osmoregulatory information from the osmoreceptors to the vasopressin (VP) and oxytocin (OT) neurons. Explants of the hypothalamo-neurohypophysial system were utilized to characterize the roles of the non-N-methyl-D-aspartate (NMDA) glutamate receptor subtypes (non-NMDA-Rs), kainic acid receptors (KA-Rs), and aminopropionic acid receptors (AMPA-Rs) and to evaluate the interdependence of NMDA-Rs and non-NMDA-Rs in eliciting hormone release. Although both KA and AMPA increased hormone release, a specific agonist of the KA-Rs, SYM-2081, was not effective. This combined with the finding that cyclothiazide, an agent that inhibits the desensitization of AMPA-Rs, increased the VP response to both KA and AMPA indicates that the increase in hormone release induced by the non-NMDA agonists is mediated via AMPA-Rs, rather than KA-Rs. Inhibition of osmotically stimulated VP and OT release by a specific AMPA-R antagonist indicated that AMPA-Rs are essential for mediating osmotically stimulated hormone release. NMDA-stimulated VP but not OT release was prevented by blockade of non-NMDA-Rs, but AMPA-stimulated VP/OT release was not prevented by NMDA-R blockade.
谷氨酸被认为是视上核（SON）中一种重要的兴奋性神经递质，参与从渗透压感受器到血管加压素（VP）和催产素（OT）神经元的渗透调节信息传递。利用下丘脑-神经垂体系统的外植体来表征非N-甲基-D-天冬氨酸（NMDA）谷氨酸受体亚型（非NMDA-Rs）、 kainic酸受体（KA-Rs）和氨基丙酸受体（AMPA-Rs）的作用，并评估NMDA-Rs和非NMDA-Rs在引发激素释放中的相互依赖性。尽管KA和AMPA均增加了激素释放，但KA-Rs的特异性激动剂SYM-2081无效。这与环噻嗪（一种抑制AMPA-Rs脱敏的药物）增加VP对KA和AMPA的反应这一发现相结合，表明非NMDA激动剂诱导的激素释放增加是通过AMPA-Rs介导的，而非KA-Rs。特异性AMPA-R拮抗剂对渗透压刺激的VP和OT释放的抑制表明，AMPA-Rs对于介导渗透压刺激的激素释放至关重要。非NMDA-Rs的阻断可阻止NMDA刺激的VP释放，但不能阻止OT释放，而NMDA-R阻断不能阻止AMPA刺激的VP/OT释放。
