自发性高血压大鼠内皮细胞中内皮素B型受体刺激增强的磷酸肌醇代谢信号转导

Enhanced phosphoinositide turnover signalling stimulated by endothelin B-type receptor in endothelial cells from spontaneously hypertensive rats.

Yokokawa K, Kohno M, Minami M, Ikeda M, Horio T, Kano H, Hanehira T, Yasunari K, Takeda T

First Deparment of Internal Medicine, Osaka City University Medical School, Japan.

Clin Exp Pharmacol Physiol Suppl. 1995 Dec;22(1):S195-6. doi: 10.1111/j.1440-1681.1995.tb02878.x.

Abstract

Endothelin (ET) B-type (ETB) receptor-mediated signal transduction was examined after stimulation with ET-3 in cultured aortic endothelial cells (EC) from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats (8 weeks old). 2. The EC from both rat strains expressed only ETB receptor mRNA. The receptor densities and affinities, which were non-selective for ET-1, -2, -3 and Sarafotoxin S6c, and mRNA expression were similar in WKY and SHR. 3. The cytosolic Ca2+ level in the absence of extracellular Ca2+, inositol 1,4,5-trisphosphate levels, protein kinase C and phospholipase C activities in response to ET-3 were greater in SHR EC than in WKY EC. 4. The 45Ca uptake in response to ET-3, which was blocked by Ni2+, was smaller in SHR EC than in WKY EC. 5. The 6-keto-PGF1alpha production was augmented in SHR, though nitric oxide formation after stimulation with ET-3 was similar. 6. These results suggest that ETB receptor-mediated phosphoinositide turnover signalling is augmented in SHR EC through postreceptor mechanism.

摘要

用ET-3刺激来自自发性高血压（SHR）大鼠和Wistar-Kyoto（WKY）大鼠（8周龄）的培养主动脉内皮细胞（EC）后，检测内皮素（ET）B型（ETB）受体介导的信号转导。2. 两种大鼠品系的EC均仅表达ETB受体mRNA。WKY和SHR的受体密度和亲和力对ET-1、-2、-3和Sarafotoxin S6c无选择性，且mRNA表达相似。3. 对ET-3反应时，SHR EC中细胞外无Ca2+时的胞质Ca2+水平、肌醇1,4,5-三磷酸水平、蛋白激酶C和磷脂酶C活性均高于WKY EC。4. 对ET-3反应的45Ca摄取（被Ni2+阻断）在SHR EC中比在WKY EC中小。5. SHR中6-酮-PGF1α生成增加，尽管ET-3刺激后的一氧化氮形成相似。6. 这些结果表明，ETB受体介导的磷酸肌醇代谢信号转导在SHR EC中通过受体后机制增强。