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

Neuropharmacology. 2000 Jan 28;39(3):482-96. doi: 10.1016/s0028-3908(99)00141-0.


ATP-induced Ca2+ 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 P2 receptors. In undifferentiated cells the ATP-induced Ca2+ response was entirely dependent on Ca2+ influx, could not 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 (InsP3). These results suggest that in undifferentiated PC12 cells ATP mainly acts on a P2X receptor, possibly the P2X4 subtype. After treatment with NGF for 7 days the ATP response was increased and partially sensitive to PPADS. A component of the ATP-induced Ca2+ increase was due to mobilisation of intracellular Ca2+ stores and another to capacitative Ca2+ entry. UTP caused an increase in intracellular Ca2+, and InsP3 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 P2Y2 subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Adenosine Triphosphate / physiology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / drug effects*
  • Calcium Channels / physiology
  • Mice
  • Nerve Growth Factor / pharmacology*
  • Nerve Growth Factor / physiology
  • PC12 Cells
  • Platelet Aggregation Inhibitors / pharmacology
  • Pyridoxal Phosphate / analogs & derivatives
  • Pyridoxal Phosphate / pharmacology
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Purinergic P2 / drug effects*
  • Receptors, Purinergic P2 / metabolism
  • Uridine Triphosphate / pharmacology*
  • Uridine Triphosphate / physiology


  • Calcium Channels
  • Platelet Aggregation Inhibitors
  • RNA, Messenger
  • Receptors, Purinergic P2
  • pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid
  • Pyridoxal Phosphate
  • Adenosine Triphosphate
  • Nerve Growth Factor
  • Calcium
  • Uridine Triphosphate