Heterogeneous calcium responses to extracellular ATP in cultured rat renal tubule cells.
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.
Dockrell
M E
ME
Cell Signalling Group, Department of Renal Medicine, GKT School of Medicine, Kings College London, Bessemer Road, London SE5 9PJ, UK.
Noor
M I
MI
James
A F
AF
Hendry
B M
BM
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
C117794:XAMR 0721; D013498:Suramin; D000255:Adenosine Triphosphate; D002118:Calcium