Yamaguchi Ken'ichi, Yamada Takaho
Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-Dori 1-757, Central district, Niigata City, Niigata 951-8510, Japan.
Brain Res Bull. 2008 Sep 5;77(1):61-9. doi: 10.1016/j.brainresbull.2008.04.009. Epub 2008 May 15.
Although the anteroventral third ventricular region (AV3V), a forebrain area essential for homeostatic responses, includes receptors for gamma-aminobutyric acid (GABA), the roles of these receptors in controlling vasopressin (AVP) secretion and related phenomena have not been clarified as yet. This study aimed to pursue this problem in conscious rats implanted with indwelling catheters. Cerebral injection sites were determined histologically. Applications of bicuculline, a GABA(A) receptor antagonist, to the AV3V induced prompt and marked augmentations in plasma AVP, osmolality, glucose, arterial pressure and heart rate, without affecting plasma electrolytes. Such phenomena did not occur when phaclofen, a GABA(B) receptor antagonist, was applied to the AV3V. All of the effects of AV3V-administered bicuculline were abolished by preadministration of the GABA(A) receptor agonist muscimol. Preadministration of either MK-801 or NBQX, ionotropic glutamatergic receptor antagonists, was also potent to abolish the AVP response to AV3V bicuculline. When hypertonic saline was infused intravenously, plasma AVP increased progressively, in parallel with rises in plasma osmolality, sodium and arterial pressure. AV3V application of muscimol or baclofen, a GABA(B) receptor agonist, was found to abolish the response of plasma AVP, without inhibiting that of the osmolality or sodium. The response of arterial pressure was also blocked by muscimol treatment, but not by baclofen treatment. Based on these results, we concluded that, under basal conditions, GABA receptors in the AV3V or vicinity may tonically operate to attenuate AVP secretion and cardiovascular functions through mechanisms associated with glutamatergic activity, and that plasma hyperosmolality may cause facilitation of AVP release by decreasing forebrain GABAergic activity.
尽管前腹侧第三脑室区域（AV3V）是体内稳态反应所必需的前脑区域，包含γ-氨基丁酸（GABA）受体，但这些受体在控制血管加压素（AVP）分泌及相关现象中的作用尚未阐明。本研究旨在通过植入留置导管的清醒大鼠来探讨这一问题。通过组织学方法确定脑内注射部位。向AV3V注射GABA(A)受体拮抗剂荷包牡丹碱后，血浆AVP、渗透压、葡萄糖、动脉压和心率迅速且显著升高，而血浆电解质不受影响。向AV3V注射GABA(B)受体拮抗剂巴氯芬时，未出现上述现象。预先给予GABA(A)受体激动剂蝇蕈醇可消除向AV3V注射荷包牡丹碱的所有效应。预先给予离子型谷氨酸能受体拮抗剂MK-801或NBQX也能有效消除AVP对向AV3V注射荷包牡丹碱的反应。静脉输注高渗盐水时，血浆AVP随着血浆渗透压、钠和动脉压的升高而逐渐增加。发现向AV3V注射蝇蕈醇或GABA(B)受体激动剂巴氯芬可消除血浆AVP反应，而不抑制渗透压或钠的反应。蝇蕈醇处理可阻断动脉压反应，而巴氯芬处理则不能。基于这些结果，我们得出结论，在基础条件下，AV3V或其附近的GABA受体可能通过与谷氨酸能活性相关的机制进行紧张性调节，以减弱AVP分泌和心血管功能，并且血浆高渗可能通过降低前脑GABA能活性促进AVP释放。
