Yamaguchi Ken'ichi, Watanabe Kazuo
Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-Dori 1-757, Niigata City 951-8510, Japan.
Brain Res Bull. 2004 May 30;63(4):321-9. doi: 10.1016/j.brainresbull.2004.04.002.
This study aimed to evaluate the roles of metabotropic glutamate receptors (mGluRs) in the anteroventral third ventricular region (AV3V; a pivotal area for osmotic responses and PGE2 actions) in regulating AVP secretion and cardiovascular function. In conscious and unrestrained rats, we examined the effects of AV3V infusion of t-ACPD (an agonist for mGluRs) and 8-bromo (Br)-cAMP (an agonist for cAMP associated with mGluR action) on plasma and cardiovascular variables, and the effects of MCPG (an antagonist for mGluRs) on the responses to t-ACPD, PGE2, and hyperosmolality. AV3V infusion of t-ACPD or 8-Br-cAMP produced dose-dependent rises in plasma AVP, arterial pressure and heart rate after 5 or 15 min, without altering plasma osmolality, sodium, potassium or chloride. t-ACPD administration into the cerebral ventricle had no effects on the variables. The plasma AVP and arterial pressure responses to AV3V t-ACPD infusion were blocked by preadministration of MCPG 15 min before the infusion. MCPG treatment was also potent at inhibiting the augmentation of plasma AVP elicited by AV3V infusion of PGE2, although its pressor and tachycardiac actions were not influenced. MCPG application, however, had no effect on either the increases in plasma AVP or arterial pressure in response to the enhanced plasma osmolality induced by i.v. infusion of hypertonic saline or their stable levels during isotonic saline infusion. Histological analysis showed that the AV3V drug infusion sites were located in structures such as the median or medial preoptic nucleus and periventricular nucleus. These results suggest that AV3V mGluRs may act to potentiate AVP release and cardiovascular function when stimulated in the basal state, and may participate in the hormone secretion prompted by AV3V PGE2, despite probable negligible contributions to the mechanisms responsible for the PGE2 cardiovascular effects or the phenomenon provoked by osmotic load.
本研究旨在评估代谢型谷氨酸受体(mGluRs)在前腹侧第三脑室区域(AV3V;渗透反应和前列腺素E2作用的关键区域)在调节抗利尿激素(AVP)分泌和心血管功能中的作用。在清醒且不受束缚的大鼠中,我们研究了向AV3V注入反式-1-氨基环丙烷-1,3-二羧酸(t-ACPD,一种mGluRs激动剂)和8-溴(Br)-环磷腺苷(8-Br-cAMP,一种与mGluR作用相关的cAMP激动剂)对血浆和心血管变量的影响,以及甲基环己基哌啶酮(MCPG,一种mGluRs拮抗剂)对t-ACPD、前列腺素E2和高渗刺激反应的影响。向AV3V注入t-ACPD或8-Br-cAMP在5或15分钟后可使血浆AVP、动脉血压和心率呈剂量依赖性升高,而不改变血浆渗透压以及钠、钾或氯的水平。向脑室注入t-ACPD对这些变量无影响。在注入前15分钟预先给予MCPG可阻断向AV3V注入t-ACPD所引起的血浆AVP和动脉血压反应。MCPG处理也能有效抑制向AV3V注入前列腺素E2所引起的血浆AVP升高,尽管其升压和心动过速作用未受影响。然而,MCPG应用对静脉输注高渗盐水引起的血浆渗透压升高所导致的血浆AVP增加或动脉血压升高,以及等渗盐水输注期间它们的稳定水平均无影响。组织学分析表明,AV3V药物注入部位位于诸如视前正中核或内侧视前核以及室周核等结构中。这些结果表明,基础状态下受刺激时,AV3V的mGluRs可能会增强AVP释放和心血管功能,并且可能参与AV3V前列腺素E2引发的激素分泌,尽管对前列腺素E2心血管效应或渗透压负荷引发的现象的机制可能贡献微不足道。