Sakai R R, Ma L Y, He P F, Fluharty S J
Department of Animal Biology, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Regul Pept. 1995 Oct 20;59(2):183-92. doi: 10.1016/0167-0115(95)00111-n.
The central actions of the peptide hormone angiotensin II (AngII) are importantly involved in body fluid homeostasis. Included amongst these actions is a potent dipsogenic response that has been implicated in the thirst that develops during many forms of extracellular dehydration. The use of highly selective receptor antagonists has revealed that the Type 1 (AT1), and not the Type 2 (AT2), AngII receptor subtype mediates this drinking response. More recently, antisense oligonucleotides specific for the AT1 receptor have been developed and after intracerebroventricular (i.c.v.) administration, they significantly reduce the dipsogenic response elicited by a similar injection of AngII. In the present study AT1 antisense oligonucleotides were used to further investigate their effect on experimentally induced thirst in the rat. In addition, immunohistochemical analysis of biotin-labeled oligonucleotides was performed in order to correlate the behavioral effects of the oligonucleotides with their distribution in the brain. The results demonstrated that the antidipsogenic effects of the oligonucleotides were dose and time-dependent and were limited to those thirst challenges that involve activation of the renin-angiotensin system. Collectively, these results demonstrate the efficacy and behavioral specificity of these oligonucleotides, as well as their utility in investigating the physiological role of cerebral AngII receptor subpopulations in various models of thirst.
肽类激素血管紧张素II（AngII）的中枢作用在体液平衡中起着重要作用。这些作用包括一种强烈的致渴反应，这种反应与多种形式的细胞外脱水过程中出现的口渴有关。使用高度选择性受体拮抗剂已表明，是1型（AT1）而非2型（AT2）血管紧张素II受体亚型介导这种饮水反应。最近，已开发出针对AT1受体的反义寡核苷酸，经脑室内（i.c.v.）给药后，它们能显著降低类似注射血管紧张素II所引发的致渴反应。在本研究中，使用AT1反义寡核苷酸进一步研究它们对实验诱导的大鼠口渴的影响。此外，对生物素标记的寡核苷酸进行了免疫组织化学分析，以便将寡核苷酸的行为效应与其在脑中的分布联系起来。结果表明，寡核苷酸的抗致渴作用具有剂量和时间依赖性，且仅限于那些涉及肾素 - 血管紧张素系统激活的口渴刺激。总体而言，这些结果证明了这些寡核苷酸的有效性和行为特异性，以及它们在研究脑内血管紧张素II受体亚群在各种口渴模型中的生理作用方面的效用。
