Insulin Induces Internalization of the Plasma Membrane 5-Hydroxytryptamine2A (5-HT2A) Receptor in the Isolated Human Endothelium-Denuded Saphenous Vein via the Phosphatidylinositol 3-Kinase Pathway

Journal of Pharmacological Sciences

Eisaku Nakamura⁴  Ryuichi Yamamoto¹  Shuji Gamoh¹  Yujiro Asada³  Akito Suzuki²  Masachika Kuwabara⁶  Hiroaki Hisa⁵  Naoko Tanaka-Totoribe¹  Tasuku Kanai¹  Yasuko Matsuo¹ 

[1] First Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan;Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan;Department of Pathology, Faculty of Medicine, Miyazaki University, Japan;Department of Cardiovascular Surgery, Miyazaki Prefectural Nobeoka Hospital, Japan;Second Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan;Kuwabara Clinic, Japan

关键词: insulin-induced vasorelaxation;    saphenous vein (SV);    internalization of 5-HT2A receptor;    diabetes mellitus (DM);    nitric oxide (NO);   

DOI  :  10.1254/jphs.11172FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(24)Cited-By(4)The aim of this study was to investigate the relaxant effect of insulin on the 5-hydroxytryptamine (5-HT)-induced constriction of the human endothelium-denuded saphenous vein (SV) and its signal transduction pathway. During the 5-HT-induced sustained constriction of vessels, insulin induced vasorelaxation in a concentration-dependent manner. This insulin-induced vasorelaxation was partially attenuated by L-NAME, a nitric oxide synthase (NOS) inhibitor, and was abolished by wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor. Insulin increased the Ser473 phosphorylation of Akt. Endothelial NOS and inducible NOS protein expressions were observed in SV smooth muscle when insulin induced relaxation of SV vessels preconstricted with 5-HT. Although insulin did not affect the total protein level of 5-HT2A receptors, it decreased the particulate protein level and reciprocally increased the soluble protein level of 5-HT2A receptors in a concentration-dependent manner. These results demonstrate that insulin can induce the internalization of 5-HT2A receptors from the plasma membrane to the cytoplasm. The insulin-induced internalization of 5-HT2A receptors was abolished by wortmannin but was not affected by L-NAME. These results suggest that the relaxant effect of insulin on 5-HT-induced vasoconstriction is mediated in part by the internalization of plasma membrane 5-HT2A receptors and the production of nitric oxide via the PI3-K/Akt pathway.

【 授权许可】

Unknown