Eguchi T, Takano Y, Hatae T, Saito R, Nakayama Y, Shigeyoshi Y, Okamura H, Krause J E, Kamiya H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Brain Res. 1996 Dec 16;743(1-2):49-55. doi: 10.1016/s0006-8993(96)01020-7.
Studies were performed on the central antidiuretic actions via the tachykinin NK-3 receptor in the rat hypothalamic paraventricular nucleus (PVN). Microinjections of the selective tachykinin NK-3 receptor agonist senktide (2-200 pmol) into the PVN resulted in prolonged inhibition of urine output in water-loaded rats, its effect being dose-dependent. The antidiuretic action of senktide was blocked by pretreatment with the vasopressin V2 receptor antagonist OPC-31260 (1 mg/kg, i.v.), but not by microinjection of the angiotensin II AT-1 receptor antagonist losartan (1 nmol) into the PVN. NK-3 receptor mRNA was strongly detected in the magnocellular part of the PVN and the supraoptic nucleus (SON) of the hypothalamus as detected by in situ hybridization histochemistry. Moreover, [3H]senktide binding sites were also detected in the PVN and the SON by receptor autoradiography. These findings suggest that NK-3 receptors in the PVN may be involved in water regulation by stimulation of vasopressin secretion from the posterior pituitary gland, and that vasopressin caused water reabsorbtion via the kidney V2 receptor.
通过速激肽NK-3受体对大鼠下丘脑室旁核（PVN）的中枢抗利尿作用进行了研究。向PVN微量注射选择性速激肽NK-3受体激动剂senktide（2-200皮摩尔）可导致水负荷大鼠的尿量长期受到抑制，其作用呈剂量依赖性。用血管加压素V2受体拮抗剂OPC-31260（1毫克/千克，静脉注射）预处理可阻断senktide的抗利尿作用，但向PVN微量注射血管紧张素II AT-1受体拮抗剂氯沙坦（1纳摩尔）则不能阻断其作用。通过原位杂交组织化学检测发现，在PVN的大细胞部分和下丘脑视上核（SON）中强烈检测到NK-3受体mRNA。此外，通过受体放射自显影在PVN和SON中也检测到了[3H]senktide结合位点。这些发现表明，PVN中的NK-3受体可能通过刺激垂体后叶分泌血管加压素参与水调节，并且血管加压素通过肾脏V2受体引起水重吸收。
