P2Y receptors contribute to ATP-induced increases in intracellular calcium in differentiated but not undifferentiated PC12 cells

ATP-induced Ca(2+) transients were examined in individual PC12 cells of a well defined clone, before and after treatment with nerve growth factor (NGF) to induce a neurone-like phenotype. Using reverse transcriptase PCR these cells were found to express mRNA for several PZ receptors, In undifferentiated cells the ATP-induced Ca(2+) response was entirely dependent on Ca(2+) influx, could nor be mimicked by UTP, alpha,beta-methylene ATP or dibenzoyl ATP or be blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). ATP had no significant effect on levels of cyclic AMP or inositol 1,4,5-trisphosphate (InsP(3)). These results suggest that in undifferentiated PC12 cells ATP mainly acts on a P2X receptor, possibly the P2X(4) subtype, After treatment with NGF for 7 days the ATP response was increased and partially sensitive to PPADS, A component of the ATP-induced Ca(2+) increase was due to mobilisation of intracellular Ca(2+) stores and another to capacitative Ca(2+) entry, UTP caused an increase in intracellular Ca(2+), and InsP(3) formation could be stimulated by ATP and UTP, ATP also caused a small increase in cyclic AMP, but this was abolished in the presence of indomethacin. Thus, after NGF treatment ATP acts partially via a P2Y receptor, possibly the P2Y(2) subtype. (C) 2000 Elsevier Science Ltd. All rights reserved.