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. 1996 Sep;119(2):360–364. doi: 10.1111/j.1476-5381.1996.tb15994.x

The effect of PPADS as an antagonist of inositol (1,4,5)trisphosphate induced intracellular calcium mobilization.

P Vigne 1, P Pacaud 1, V Urbach 1, E Feolde 1, J P Breittmayer 1, C Frelin 1
PMCID: PMC1915870  PMID: 8886421

Abstract

1. Brain capillary endothelial cells responded to uridine 5'-triphosphate (UTP) and adenosine 5'-triphosphate (ATP) by activation of phospholipase C and by large changes in [Ca2+]i. These cells expressed mRNA sequences identical to the sequence of the P2Y2-purinoceptor of rat pituitaries. 2. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) at 100 microM did not prevent UTP and ATP induced accumulations of total [3H]-inositol (poly)phosphates. It inhibited UTP and ATP induced intracellular Ca2+ mobilization (IC50 = 30 microM) by non competitive mechanism. 3. PPADS (100 microM) inhibited endothelin-1 induced accumulation of total [3H]-inositol (poly)phosphates by less than 20% and prevented most of endothelin-1 induced intracellular Ca2+ mobilization (IC50 = 30 microM). 4. PPADS (100 microM) had no action on ionomycin induced intracellular Ca2+ mobilization. 5. Microinjection of inositol (1,4,5)trisphosphate (InsP3) into Xenopus oocytes induced large Ca2+ activated Cl- currents that were prevented by heparin and by PPADS. 6. It is concluded that PPADS does not recognize rat P2Y2-purinoceptors and prevents UTP and ATP induced intracellular Ca2+ mobilization by a non-specific mechanism that could involve the inhibition of InsP3 channels.

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Selected References

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