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

• Kanai Tasuku

  First Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan

• Kuwabara Masachika

  Kuwabara Clinic, Japan

• Tanaka-Totoribe Naoko

  First Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan

• Nakamura Eisaku

  Department of Cardiovascular Surgery, Miyazaki Prefectural Nobeoka Hospital, Japan

• Matsuo Yasuko

  First Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan

• Gamoh Shuji

  First Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan

• Suzuki Akito

  Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan

• Asada Yujiro

  Department of Pathology, Faculty of Medicine, Miyazaki University, Japan

• Hisa Hiroaki

  Second Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan

• Yamamoto Ryuichi

  First Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan

Abstract

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-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.

Journal

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 118 (2), 178-185, 2012

  The Japanese Pharmacological Society

Keywords

• insulin-induced vasorelaxation
• saphenous vein (SV)
• internalization of 5-HT<SUB>2A</SUB> receptor
• diabetes mellitus (DM)
• nitric oxide (NO)

Details

• CRID: 1390282680154729472
• NII Article ID: 10030454748
• NII Book ID: AA11806667
• DOI: 10.1254/jphs.11172fp
• ISSN: 13478648
• ISSN: 13478613
• NDL BIB ID: 023439411
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023439411
• Web Site: https://search.jamas.or.jp/link/ui/2012244782
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed