title: Purinoceptor-mediated calcium mobilization and cellular proliferation in cultured bovine corneal endothelial cells.
abstract: In the present study, we investigated the effect of adenosine triphosphate (ATP) on cytosolic free calcium mobilization and mitogenic activity in cultured bovine corneal endothelial cells (BCEC). The [Ca2+]i was determined using a Ca2+ sensitive indicator, Fura-2/AM, and cell proliferation was evaluated by counting the cell number. ATP, its metabolites and analogs caused transient increase in [Ca2+]i in a concentration-dependent manner (10(-7) M-10(-3) M) and the potency of agonists was ordered as follows: 2-methylthio-ATP > uridine triphosphate > ATP > adenosine diphosphate. Adenosine monophosphate and adenosine did not affect [Ca2+]i. ATP (10(-4) M) also promoted the accumulation of inositol trisphosphate (IP3). The ATP-induced transient [Ca2+]i increase and IP3 accumulation were attenuated by pretreatment with a phospholipase C inhibitor, U-73122 (5 microM), for 30 min. ATP (10(-5) M) significantly enhanced the proliferation of BCEC. ATP-induced [Ca2+]i increase and cell proliferation were inhibited by a purinoceptor antagonist, suramin (10(-4) M). Thus, the present study indicates that BCEC contain P2 purinoceptors that regulate their proliferation.
authors.affiliation: Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: S H
authors.initials: SH
authors.lastname: Cha
authors.forename: T W
authors.initials: TW
authors.lastname: Hahn
authors.forename: T
authors.initials: T
authors.lastname: Sekine
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Endou
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004728:Endothelium, Corneal / Q000166:cytology / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D014544:Uridine Triphosphate / Q000494:pharmacology
chemical_list: D004963:Estrenes; D011760:Pyrrolidinones; D018048:Receptors, Purinergic P2; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D000255:Adenosine Triphosphate; D002118:Calcium; D014544:Uridine Triphosphate