Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat
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 adenosin...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2011-01-01
|
| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319307583 |
| _version_ | 1828429728109821952 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Megumi Sugihara |
| collection | DOAJ |
| description | 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 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.[Supplementary materials: available only at http://dx.doi.org/10.1254/jphs.10281FP] Keywords:: uridine 5′-triphosphate (UTP), P2X receptor, TRPC3, non-selective cation channel |
| first_indexed | 2024-12-10T17:38:23Z |
| format | Article |
| id | doaj.art-6813dc7948864d5abeff809f6fccfe2d |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T17:38:23Z |
| publishDate | 2011-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-6813dc7948864d5abeff809f6fccfe2d2022-12-22T01:39:27ZengElsevierJournal of Pharmacological Sciences1347-86132011-01-011153293308Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the RatMegumi Sugihara0Hiromitsu Morita1Miho Matsuda2Hisanori Umebayashi3Shunichi Kajioka4Shinichi Ito5Motohiro Nishida6Ryosuke Inoue7Toshiko Futatsuki8Jun Yamazaki9Yasuo Mori10Ryuji Inoue11Yushi Ito12Kihachiro Abe13Masato Hirata14Special Patient Oral Care Unit, Kyushu University Hospital, Fukuoka 812-8582, Japan; Laboratory of Molecular and Cellular Biochemistry, Fukuoka 812-8582, JapanSpecial Patient Oral Care Unit, Kyushu University Hospital, Fukuoka 812-8582, Japan; Corresponding author. hmorita@dent.kyushu-u.ac.jpLaboratory of Molecular and Cellular Biochemistry, Fukuoka 812-8582, JapanLaboratory of Molecular and Cellular Biochemistry, Fukuoka 812-8582, JapanDepartment of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, JapanDepartment of Dental Anesthesiology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, JapanDepartment of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, JapanSpecial Patient Oral Care Unit, Kyushu University Hospital, Fukuoka 812-8582, JapanSpecial Patient Oral Care Unit, Kyushu University Hospital, Fukuoka 812-8582, JapanDepartment of Physiological Science & Molecular Biology, Fukuoka Dental College, Fukuoka 814-0193, JapanLaboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, JapanDepartment of Physiology, Graduate School of Medical Sciences, Fukuoka University, Fukuoka 814-0180, JapanDepartment of Health Science, Kumamoto Health Science University, Kumamoto 861-5598, JapanSpecial Patient Oral Care Unit, Kyushu University Hospital, Fukuoka 812-8582, JapanLaboratory of Molecular and Cellular Biochemistry, Fukuoka 812-8582, JapanWe 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 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.[Supplementary materials: available only at http://dx.doi.org/10.1254/jphs.10281FP] Keywords:: uridine 5′-triphosphate (UTP), P2X receptor, TRPC3, non-selective cation channelhttp://www.sciencedirect.com/science/article/pii/S1347861319307583 |
| spellingShingle | 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 Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat Journal of Pharmacological Sciences |
| title | Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat |
| title_full | Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat |
| title_fullStr | Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat |
| title_full_unstemmed | Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat |
| title_short | Dual Signaling Pathways of Arterial Constriction by Extracellular Uridine 5′-Triphosphate in the Rat |
| title_sort | dual signaling pathways of arterial constriction by extracellular uridine 5 triphosphate in the rat |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319307583 |
| work_keys_str_mv | AT megumisugihara dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT hiromitsumorita dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT mihomatsuda dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT hisanoriumebayashi dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT shunichikajioka dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT shinichiito dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT motohironishida dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT ryosukeinoue dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT toshikofutatsuki dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT junyamazaki dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT yasuomori dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT ryujiinoue dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT yushiito dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT kihachiroabe dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat AT masatohirata dualsignalingpathwaysofarterialconstrictionbyextracellularuridine5triphosphateintherat |