Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat

Journal of Pharmacological Sciences

Miho Matsuda²  Kihachiro Abe⁶  Megumi Sugihara⁶  Shinichi Ito⁹  Shunichi Kajioka⁷  Yushi Ito¹  Masato Hirata²  Jun Yamazaki⁵  Hisanori Umebayashi²  Toshiko Futatsuki⁶  Motohiro Nishida⁸  Ryuji Inoue³  Hiromitsu Morita⁶  Yasuo Mori⁴  Ryosuke Inoue⁶ 

[1] Department of Health Science, Kumamoto Health Science University, Japan;Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Japan;Department of Physiology, Graduate School of Medical Sciences, Fukuoka University, Japan;Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Japan;Department of Physiological Science & Molecular Biology, Fukuoka Dental College, Japan;Special Patient Oral Care Unit, Kyushu University Hospital, Japan;Department of Urology, Graduate School of Medical Sciences, Kyushu University, Japan;Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, Japan;Department of Dental Anesthesiology, Faculty of Dental Science, Kyushu University, Japan

关键词: uridine 5′-triphosphate (UTP);    P2X receptor;    TRPC3;    non-selective cation channel;   

DOI  :  10.1254/jphs.10281FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(58)Cited-By(2)Supplementary materials(3)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]

【 授权许可】

Unknown