2012年
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
Journal of Pharmacological Sciences
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- 巻
- 118
- 号
- 2
- 開始ページ
- 178
- 終了ページ
- 185
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1254/jphs.11172FP
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.
- ID情報
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- DOI : 10.1254/jphs.11172FP
- ISSN : 1347-8613
- ISSN : 1347-8648
- PubMed ID : 22293289
- SCOPUS ID : 84857510205