Orexin Receptor Type-1 Couples Exclusively to Pertussis Toxin-Insensitive G-Proteins, while Orexin Receptor Type-2 Couples to Both Pertussis Toxin-Sensitive and *Insensitive G-Proteins
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概要
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Signal transduction pathways of orexin receptors were examined using a nerve-like cell line transfected with orexin receptor type-1 (OX1R) and orexin receptor type-2 (OX2R). Forskolin-stimulated cyclic adenosine 3,5-monophosphate (cAMP) accumulation in OX2R-expressing cells was inhibited by orexin in a dose-dependent manner, and the effect was abolished by pretreatment with pertussis toxin (PTX). The inhibitory effect of orexin on forskolin-stimulated cAMP accumulation was not observed in OX1R-expressing cells. Administration of orexin to these cells resulted in a transient increase of intracellular calcium concentration ([Ca2+]i). Orexin-stimulated increases in [Ca2+]i in OX1R- or OX2R-expressing cells were not affected by the PTX pretreatment. These observations suggest that OX1R couples exclusively to PTX-insensitive G-proteins, while OX2R couples to both PTX-sensitive and -insensitive G-proteins. To examine the relative contributions of these G-proteins in OX2R-mediated activation of neurons, we used histaminergic tuberomammillary nucleus neurons, in which OX2R is abundantly expressed. We found that a phospholipase C (PLC)-inhibitor, U73122, inhibits orexin-mediated neuronal activation, but PTX showed no effect on it. This suggests that although OX2R couples to multiple G-proteins, activation of neurons by orexins through OX2R is mediated via a PTX-insensitive, PLC dependent pathway.
- 社団法人 日本薬理学会の論文
- 2003-07-01
著者
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三輪 佳宏
筑波大学大学院人間総合科学研究科生命システム医学専攻
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Goto Katsutoshi
Departments of Internal Medicine, Surgery, Pharmacology, University of Tsukuba
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Takeyama Youichi
横浜栄共済病院 内科循環器内科
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Goto Katsutoshi
Department Of Pharmacology Institute Of Basic Medical Sciences University Of Tsukuba
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MIWA Yoshihiro
Department of Molecular Pharmacology, Graduate School of Comprehensive Human Sciences, University of
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YADA Toshihiko
Department of Physiology, Jichi Medical School
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Yada Toshihiko
Department Of Physiology Division Of Integrative Physiology Jichi Medical School School Of Medicine
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Goto Katsutoshi
Department Of Pharmacology Institute Of Basic Medical Sciences The University Of Tsukuba
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Miwa Yoshihiro
Department Of Dintistry The University Of Tokushima
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Sakura Takeshi
Department Of Pharmacology Institute Of Basic Medical Sciences University Of Tsukuba
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ZHU Yun
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba
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YAMANAKA Akihiro
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba
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SHIBAHARA Megumi
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba
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ABE Yoichiro
Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba
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Miwa Yoshihiro
Department Of Biochemistry School Of Dentistry The University Of Tokushima
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Zhu Yun
Department Of Forensic Medicine Medical School Of Zhengzhou University
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Zhu Yun
Department Of Pharmacology Institute Of Basic Medical Sciences University Of Tsukuba
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Abe Yoichiro
Department Of Pharmacology Institute Of Basic Medical Sciences University Of Tsukuba
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Yamanaka Akihiro
Department Of Pharmacology Institute Of Basic Medical Sciences University Of Tsukuba
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Shibahara Megumi
Department Of Pharmacology Institute Of Basic Medical Sciences University Of Tsukuba
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Goto Katsutoshi
Department Of Ophthalmology Kawasaki Medical School
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YAMANAKA Akihiro
Department of Nuclear Engineering, Faculty of Engineering, Kyushu University
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