title: Dual signaling pathways of arterial constriction by extracellular uridine 5'-triphosphate in the rat.
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 P2X(1) 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 µM) provoked a dose-dependent contraction of de-endothelialized aortic ring preparation consisting of phasic and tonic components. Removal of extracellular Ca(2+) 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 [Ca(2+)](i) were also evoked by UTP in rat aortic myocytes. In contrast to the low expression of TRPC3, significant expression of P2X(1) 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 P2X(1)-like and P2Y receptors, but not TRPC3.
authors.affiliation: Special Patient Oral Care Unit, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Sugihara
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Morita
authors.forename: Miho
authors.initials: M
authors.lastname: Matsuda
authors.forename: Hisanori
authors.initials: H
authors.lastname: Umebayashi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kajioka
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ito
authors.forename: Motohiro
authors.initials: M
authors.lastname: Nishida
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Inoue
authors.forename: Toshiko
authors.initials: T
authors.lastname: Futatsuki
authors.forename: Jun
authors.initials: J
authors.lastname: Yamazaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.forename: Ryuji
authors.initials: R
authors.lastname: Inoue
authors.forename: Yushi
authors.initials: Y
authors.lastname: Ito
authors.forename: Kihachiro
authors.initials: K
authors.lastname: Abe
authors.forename: Masato
authors.initials: M
authors.lastname: Hirata
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001158:Arteries / Q000502:physiology*; D002118:Calcium / Q000032:analysis; D003250:Constriction; D005110:Extracellular Space / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D058910:Purinergic P2 Receptor Agonists / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D012313:RNA / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D012313:RNA; D002118:Calcium; D014544:Uridine Triphosphate