Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat
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概要
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We investigated actions of uridine 5′-triphosphate (UTP) in rat aorta, cerebral and mesenteric arteries, and their single myocytes. UTP (≥10 μM) elicited an inward-rectifying current strongly reminiscent of activation of P2X1 receptor, and a similar current was also induced by α,β-methylene adenosine 5′-triphosphate (ATP) (≥100 nM). UTP desensitized α,β-methylene ATP–evoked current, and vice versa. The UTP-activated current was insensitive to G-protein modulators, TRPC3 inhibitors, or TRPC3 antibody, but was sensitive to P2-receptor inhibitors or P2X1-receptor antibody. Both UTP (1 mM) and α,β-methylene ATP (10 μM) elicited similar conductance single channel activities. UTP (≥10 μM) provoked a dose-dependent contraction of de-endothelialized aortic ring preparation consisting of phasic and tonic components. Removal of extracellular Ca2+ or bath-applied 2′,3′-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) (30 μM) or nifedipine (10 μM) completely inhibited the phasic contraction while only partially reducing the tonic one. The tonic contraction was almost completely abolished by additional application of thapsigargin (2 μM). Similar biphasic rises in [Ca2+]i were also evoked by UTP in rat aortic myocytes. In contrast to the low expression of TRPC3, significant expression of P2X1 receptor was detected in all arteries by RT-PCR and immunoblotting, and its localization was limited to plasma membrane of myocytes as indicated by immunohistochemistry. These results suggest that UTP dually activates P2X1-like and P2Y receptors, but not TRPC3.[Supplementary materials: available only at http://dx.doi.org/10.1254/jphs.10281FP]
著者
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ITO Shinichi
Department of Pediatrics and Child Health, Kurume University School of Medicine
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Inoue Ryuji
Department of Physiology, School of Medicine, Fukuoka University
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Nishida Motohiro
Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu Univer
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ITO Yushi
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University
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Yamazaki Jun
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Japan
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MORI Yasuo
Laboratory of Molecular Biology, Department of Synthetic and Biological Chemistry, Graduate School o
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ABE Kihachiro
Special Patient Oral Care Unit, Kyushu University Hospital
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HIRATA Masato
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collabo
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Inoue Ryuji
Department Of Pharmacology Faculty Of Medicine Kyushu University
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Hirata Masato
Laboratory Of Molecular And Cellular Biochemistry Faculty Of Dental Science And Station For Collabor
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Abe Kihachiro
Special Patient Oral Care Unit Kyushu University Hospital
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Sugihara Megumi
Special Patient Oral Care Unit, Kyushu University Hospital, Japan
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Morita Hiromitsu
Special Patient Oral Care Unit, Kyushu University Hospital, Japan
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Matsuda Miho
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Jap
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Umebayashi Hisanori
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Jap
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Kajioka Shunichi
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Japan
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Inoue Ryosuke
Special Patient Oral Care Unit, Kyushu University Hospital, Japan
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Futatsuki Toshiko
Special Patient Oral Care Unit, Kyushu University Hospital, Japan
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Ito Yushi
Department Of Neonatology National Center For Child Health And Development
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Nishida Motohiro
Department Of Pharmacology And Toxicology Graduate School Of Pharmaceutical Sciences Kyushu Universi
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Umebayashi Hisanori
Laboratory Of Molecular And Cellular Biochemistry Faculty Of Dental Science And Station For Collabor
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Yamazaki Jun
Department Of Pharmacology Fukuoka Dental College
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Mori Yasuo
Laboratory Of Food Chemistry Faculty Of Fisheries Kagoshima University
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Futatsuki Toshiko
Special Patient Oral Care Unit Kyushu University Hospital
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Kajioka Shunichi
Department Of Urology Graduate School Of Medical Sciences Kyushu University
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Nishida Motohiro
Department Of Pharmacology And Toxicology Faculty Of Pharmaceutical Sciences Kyushu University
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Morita Hiromitsu
Special Patient Oral Care Unit Kyushu University Hospital
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Matsuda Miho
Laboratory Of Molecular And Cellular Biochemistry Faculty Of Dental Science Kyushu University
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Ito Shinichi
Department Of Dental Anesthesiology Faculty Of Dental Science Kyushu University
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