title: Mitochondria play an important role in adenosine-induced ATP release from Madin-Darby canine kidney cells.
abstract: We previously found that adenosine stimulates ATP release from Madin-Darby canine kidney (MDCK) cells, by activating an Ins(1,4,5)P(3) sensitive-calcium (Ca(2+)) pathway through the stimulation of A(1) receptors. Thus, we investigated the intracellular pathway of ATP efflux after the rise in intracellular Ca(2+) in MDCK cells. Adenosine evoked an increase in mitochondrial Ca(2+) using Rhod-2/AM, a mitochondrial Ca(2+) indicator. Adenosine-induced ATP release was inhibited by mitochondrial modulators, such as oxidative phosphorylation modulators (carbonyl cyanide 3-chlorophenylhydrazone and oligomycin), mitochondrial ADP/ATP carrier inhibitors (N-ethylmaleimide, carboxyatractyloside and bongkrekic acid), a mitochondrial Na(+)-Ca(2+) exchange inhibitor (CGP-37157). In addition, mitochondrial modulators significantly reduced intracellular ATP content. On the other hand, 2-deoxy-glucose (2-DG) induced a greater decrease in intracellular ATP content than mitochondrial modulators. ATP release was still induced by adenosine in the presence of 5mM 2-DG. These results suggest that mitochondria play an important role in the signaling pathway of adenosine-triggered ATP release in MDCK cells.
authors.affiliation: Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka, Japan. migitak@cis.fukuoka-u.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Migita
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhao
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; D003847:Deoxyglucose / Q000494:pharmacology; D004285:Dogs; D007668:Kidney / Q000166:cytology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D000241:Adenosine; D002118:Calcium