Radioligand Binding Characteristics of the Endothelin Receptor in the Rabbit Iris

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概要

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• We previously suggested the presence of functionally atypical endothelin (ET) A receptors in the rabbit iris sphincter. Here, we further characterized the ET receptor by a radioligand-receptor binding study utilizing a membrane fraction of the rabbit iris. In addition, we functionally confirm the presence of an atypical ETA receptor in the iris dilator similar to that in the iris sphincter. In binding experiments, [125I]ET-1 was completely displaced by ET-3 in a biphasic fashion, but only partially by BQ-123 and ETB ligands. In the presence of RES-701, ET-3 and sarafotoxin (SRTX)-b completely displaced [125I]ET-1 in a monophasic fashion, but with shallow slopes. Moreover, ET-1, ET-3 and SRTX-b completely displaced [3H]BQ-123 with IC50 values of 0.8, 81 and 4.4 nM, respectively, but with slopes of ET-3 and SRTX-b being again shallow. In iris dilator muscles, ET-3 showed lower and SRTX-b showed higher contractile activities than ET-1. SRTX-c was inactive. BQ-123 more preferentially antagonized ET-3 and SRTX-b than ET-1, with the Schild plot slope of SRTX-b being shallow. Thus, functional experiments suggested the presence of atypical ETA receptors in the iris dilator similar to the iris sphincter. However, the binding experiments suggested the presence of rather typical ETA- and ETB-like receptors. Therefore, we apparently failed to show ET binding sites corresponding to functionally atypical ETA receptors.

• 社団法人 日本薬理学会の論文

著者

• ISHIKAWA Hitoshi

  Department of Radiation Oncology, Gunma University Graduate school of Medicine

• ISHIKAWA Satoshi

  Department of Marine Bioscience, Ocean Research Institute, The University of Tokyo

• Ishikawa Satoshi

  Department Of Fishery School Of Marine Science And Technology Tokai University

• YOSHITOMI Takeshi

  Department of Ophthalmology, Akita University Faculty of Medicine

• Ishikawa Hitoshi

  Department Of Orthopedic Surgery Kobe University School Of Medicine

• Ishikawa Satoshi

  Department Of Ophthalmology Kitasato University School Of Medicine

• Ishikawa Hitoshi

  Department Of Orthoptics And Visual Science School Of Allied Health Kitasato University

• Kase Hiroshi

  Department Of Biochemistry Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.

• Yoshitomi T

  Department Of Ophthalmology Akita University

• Yoshitomi Takeshi

  Department Of Ophthalmology Akita University Faculty Of Medicine

• HARADA Yoshiteru

  Department of Pharmacology, Kitasato University School of Medicine

• NOSAKA Chihiro

  Department of Biochemistry, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd.

• HARUNO Isao

  Department of Ophthalmology, Kitasato University School of Medicine

• Harada Yoshiteru

  Department Of Pharmacology Kitasato University School Of Medicine

• Nosaka Chihiro

  Department Of Biochemistry Pharmaceutical Research Institute Kyowa Hakko Kogyo Co. Ltd.

• Haruno Isao

  Department Of Ophthalmology Kitasato University School Of Medicine

• Ishikawa Satoshi

  Department Of Earth And Planetary Sciences Kyushu University

• Ishikawa Hitoshi

  Department Of Mechanical Engineering Tokyo University Of Science

• Ishikawa Satoshi

  Department Of Chemistry Faculty Of Integrated Arts And Sciences The University Of Tokushima

• Ishikawa Hitoshi

  Kitasato Univ. Kanagawa Jpn

• ISHIKAWA Satoshi

  Departmant of Civil and Environmental Engineering, Yamanashi University

• Ishikawa Hitoshi

  Department of Electrical Engineering, College of Science and Technology, Nihon University, Chiyoda, Tokyo 101-8308, Japan

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