Lysophosphatidylcholine potentiates Ca2+ influx, pore formation and p44/42 MAP kinase phosphorylation mediated by P2X7 receptor activation in mouse microglial cells

J Neurochem. 2007 Sep;102(5):1518-1532. doi: 10.1111/j.1471-4159.2007.04570.x. Epub 2007 Apr 16.

Abstract

The P2X7 receptor (P2X7R) is an ATP-gated ion channel highly expressed in microglia. P2X7R plays important roles in inflammatory responses in the brain. However, little is known about the mechanisms regulating its functions in microglia. Lysophosphatidylcholine (LPC), an inflammatory phospholipid that promotes microglial activation, may have some relevance to P2X7R signaling in terms of microglial function. In this study, we examined its effects on P2X7R signaling in a mouse microglial cell line (MG6) and primary microglia. LPC facilitated the sustained increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) through P2X7R channels activated by ATP or BzATP. The potentiated increase in [Ca(2+)](i) was actually inhibited by P2X7R antagonists, brilliant blue G and oxidized ATP. The potentiating effect of LPC was not observed with P2Y receptor systems, which are also expressed in MG6 cells. G2A, a receptor for LPC, was expressed in MG6 cells, but not involved in the facilitating effect of LPC on the P2X7R-mediated change in [Ca(2+)](i). Furthermore, LPC enhanced the P2X7R-associated formation of membrane pores and the activation of p44/42 mitogen-activated protein kinase. These results suggest that LPC may regulate microglial functions in the brain by enhancing the sensitivity of P2X7R.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Animals, Newborn
  • Benzenesulfonates / pharmacology
  • Calcium / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Flow Cytometry / methods
  • Gene Expression Regulation / drug effects
  • Lysophosphatidylcholines / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Purinergic P2 Receptor Antagonists
  • RNA, Messenger / biosynthesis
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Purinergic P2 / physiology*
  • Receptors, Purinergic P2X7
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • Benzenesulfonates
  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • G2A receptor
  • Lysophosphatidylcholines
  • P2rx7 protein, mouse
  • Purinergic P2 Receptor Antagonists
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
  • Adenosine Triphosphate
  • Mitogen-Activated Protein Kinase 1
  • brilliant blue
  • Calcium