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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.