Insulin induces internalization of the plasma membrane 5- hydroxytryptamine 2A (5-HT 2A) receptor in the isolated human endothelium-denuded saphenous vein via the phosphatidylinositol 3-kinase pathway

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 ser 473 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-ht 2a receptors,it decreased the particulate protein level and reciprocally increased the soluble protein level of 5-ht 2a receptors in a concentration-dependent manner. these results demonstrate that insulin can induce the internalization of 5-ht 2a receptors from the plasma membrane to the cytoplasm. the insulin-induced internalization of 5-ht 2a 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-ht 2a receptors and the production of nitric oxide via the pi3-k/akt pathway. © the japanese pharmacological society.