title: Adenosine induces ATP release via an inositol 1,4,5-trisphosphate signaling pathway in MDCK cells.
abstract: ATP is released into extracellular space as an autocrine/paracrine molecule by mechanical stress and pharmacological-receptor activation. Released ATP is partly metabolized by ectoenzymes to adenosine. In the present study, we found that adenosine causes ATP release in Madin-Darby canine kidney cells. This release was completely inhibited by CPT (an A1 receptor antagonist), U-73122 (a phospholipase C inhibitor), 2-APB (an inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) receptor blocker), thapsigargin (a Ca2+-ATPase inhibitor), and BAPTA/AM (an intracellular Ca2+ chelator), but not by DMPX (an A2 receptor antagonist). However, forskolin, epinephrine, and isoproterenol, inducers of cAMP accumulation, failed to release ATP. Adenosine increased intracellular Ca2+ concentrations that were strongly blocked by CPT, U-73122, 2-APB, and thapsigargin. Moreover, adenosine enhanced accumulations of Ins(1,4,5)P3 that were significantly reduced by U-73122 and CPT. These data suggest that adenosine induces the release of ATP by activating an Ins(1,4,5)P3 sensitive-Ca2+ pathway through the stimulation of A1 receptors.
authors.affiliation: Department of Pharmacology, School of Medicine [corrected] Fukuoka University, Fukuoka 814-0180, Japan. migitak@cis.fukuoka-u.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Migita
authors.forename: Lei
authors.initials: L
authors.lastname: Lu
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kenji
authors.initials: K
authors.lastname: Honda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Kita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katsuragi
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine; D002118:Calcium