Dual signaling pathways of arterial constriction by extracellular uridine 5′-triphosphate in the rat

Megumi Sugihara, Hiromitsu Morita, Miho Matsuda, Hisanori Umebayashi, Shunichi Kajioka, Shinichi Ito, Motohiro Nishida, Ryosuke Inoue, Toshiko Futatsuki, Jun Yamazaki, Yasuo Mori, Ryuji Inoue, Yushi Ito, Kihachiro Abe, Masato Hirata

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Abstract

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 P2X 1-receptor antibody. Both UTP (1 mM) and α,β-methylene ATP (10 μM) elicited similar conductance single channel activities. UTP (≥10 ≥M) provoked a dose-dependent contraction of deendothelialized 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.

Original languageEnglish
Pages (from-to)293-308
Number of pages16
JournalJournal of Pharmacological Sciences
Volume115
Issue number3
DOIs
Publication statusPublished - Mar 24 2011

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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    Sugihara, M., Morita, H., Matsuda, M., Umebayashi, H., Kajioka, S., Ito, S., Nishida, M., Inoue, R., Futatsuki, T., Yamazaki, J., Mori, Y., Inoue, R., Ito, Y., Abe, K., & Hirata, M. (2011). Dual signaling pathways of arterial constriction by extracellular uridine 5′-triphosphate in the rat. Journal of Pharmacological Sciences, 115(3), 293-308. https://doi.org/10.1254/jphs.10281FP