title: Heterogeneous calcium responses to extracellular ATP in cultured rat renal tubule cells.
abstract: There is increasing evidence that extracellular ATP acting on purinoceptors may play an important signalling role in renal epithelial cells, often through alterations in cellular Ca(2+). In this paper effects of extracellular ATP and related purinoceptor agonists and antagonists on [Ca(2+)](i) have been studied in single cells from primary cultures of rat proximal tubule cells. Responses to 1--100 micromol/l ATP were heterogeneous; 55% of cells showed a transient rise in [Ca(2+)](i), 20% of cells showed a transient fall; in 25% there was no response. ATP actions on [Ca(2+)](i) were abolished by pre-treatment with thapsigargin. The P(2) receptor antagonist suramin unexpectedly increased the [Ca(2+)](i) response to ATP; the related antagonist XAMR 0721 did not significantly alter ATP responses. This difference is likely to arise from the inhibition of ATP hydrolysis by suramin. UTP, ADP and the non-hydrolyzable ATP analogue adenosine-5'-O-(3-thio)-triphosphate (ATP gamma S)produced similar increases in [Ca(2+)](i). The magnitude of the [Ca(2+)](i) responses to 100 micromol/l agonist gave an agonist potency order of ATP> or =ADP> or =UTP approximately ATP gamma S. Desensitisation experiments demonstrated the presence of more than one P2Y ATP receptor subtype on a single cell. These results are consistent with the expression of purinoceptors of both P2Y(1) and P2Y(2) subclasses on individual rat proximal tubule cells coupled to inositol trisphosphate-mediated release of intracellular calcium stores.
authors.affiliation: Cell Signalling Group, Department of Renal Medicine, GKT School of Medicine, Kings College London, Bessemer Road, London SE5 9PJ, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Dockrell
authors.forename: M I
authors.initials: MI
authors.lastname: Noor
authors.forename: A F
authors.initials: AF
authors.lastname: James
authors.forename: B M
authors.initials: BM
authors.lastname: Hendry
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013498:Suramin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C117794:XAMR 0721; D013498:Suramin; D000255:Adenosine Triphosphate; D002118:Calcium