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向水负荷、乙醇麻醉大鼠的下丘脑室旁核注射嘌呤受体激动剂后的抗利尿作用

Antidiuretic effects of purinoceptor agonists injected into the hypothalamic paraventricular nucleus of water-loaded, ethanol-anesthetized rats.

作者信息

Mori M, Tsushima H, Matsuda T

机构信息

Department of Pharmacology, Nagoya City University Medical School, Japan.

出版信息

Neuropharmacology. 1992 Jun;31(6):585-92. doi: 10.1016/0028-3908(92)90191-q.

DOI:10.1016/0028-3908(92)90191-q
PMID:1407398
Abstract

The effects of injection of various purinoceptor agonists into the hypothalamic paraventricular nucleus in water-loaded and ethanol-anesthetized rats were investigated. Adenosine triphosphate (ATP), beta,gamma-methyleneadenosine 5'-triphosphate (AMP-PCP) and beta,gamma-imidoadenosine 5'-triphosphate (AMP-PNP) potently decreased the outflow of urine in a time- and dose-dependent manner. The ED50 values were approx 70 and 37 nmol for ATP and AMP-PCP, respectively. Adenosine diphosphate (ADP), AMP and adenosine reduced the outflow of urine much less than ATP. Adenosine triphosphate induced concomitant increases in the osmotic pressure of the urine and in the level of arginine-vasopressin (AVP) in plasma. The antidiuretic effect of ATP was blocked by prior injection of quinidine (a P2-purinoceptor antagonist) into the paraventricular nucleus, but not by the prior injection of theophylline (a P1-purinoceptor antagonist). The effect of ATP was also blocked by intravenous injection of an AVP(V1V2)-receptor antagonist, d(CH2)5-D-Tyr(Et)VAVP. The results suggest that ATP injected into the paraventricular nucleus may stimulate a purinoceptor, releasing AVP and inducing the antidiuretic effect through renal AVP(V2) receptors.

摘要

研究了在水负荷和乙醇麻醉的大鼠下丘脑室旁核中注射各种嘌呤受体激动剂的作用。三磷酸腺苷(ATP)、β,γ-亚甲基腺苷5'-三磷酸(AMP-PCP)和β,γ-亚氨基腺苷5'-三磷酸(AMP-PNP)以时间和剂量依赖性方式显著减少尿量流出。ATP和AMP-PCP的ED50值分别约为70和37 nmol。二磷酸腺苷(ADP)、AMP和腺苷减少尿量流出的程度远小于ATP。ATP导致尿液渗透压和血浆中精氨酸加压素(AVP)水平同时升高。预先向室旁核注射奎尼丁(一种P2嘌呤受体拮抗剂)可阻断ATP的抗利尿作用,但预先注射茶碱(一种P1嘌呤受体拮抗剂)则不能。静脉注射AVP(V1V2)受体拮抗剂d(CH2)5-D-Tyr(Et)VAVP也可阻断ATP的作用。结果表明,注射到室旁核的ATP可能刺激嘌呤受体,释放AVP并通过肾AVP(V2)受体诱导抗利尿作用。

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