Ecto‐nucleotide pyrophosphatase modulates the purinoceptor‐mediated signal transduction and is inhibited by purinoceptor antagonists

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Abstract
The effect of ecto‐nucleotide pyrophosphatase (ecto‐NPPase; EC 3.6.1.9) on the ATP‐ and ADP‐mediated receptor activation was studied in rat C6 glioma cells. The P2‐purinoceptor antagonists pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) and reactive blue (RB2) are potent inhibitors (IC50=12±3 μM) of the latter enzyme. 4,4′‐diisothiocyanatostilbene‐2,2′ disulfonic acid (DIDS), 5′‐phosphoadenosine 3′‐phosphate (PAP) and suramin were less potent inhibitors with an IC50 of 22±4, 36±7 and 72±11 μM respectively. P1‐purinoceptor antagonists CGS 15943, cyclo‐pentyl theophylline (CTP) and theophylline did not affect the activity of the ecto‐NPPase. ATP‐ and ADP‐mediated P2Y1‐like receptor activation inhibited the (−)‐isoproterenol‐induced increase of intracellular cyclic AMP concentration. PPADS, an ineffective P2Y‐antagonist in C6, potentiated the ATP and ADP effect approximately 3 fold due to inhibition of nucleotide hydrolysis by the ecto‐NPPase. We conclude that ecto‐NPPase has a modulatory effect on purinoceptor‐mediated signalling in C6 glioma cell cultures. British Journal of Pharmacology (2000) 130, 139–145; doi:10.1038/sj.bjp.0703289

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