Arachidonic acid in astrocytes blocks Ca(2+) oscillations by inhibiting store-operated Ca(2+) entry, and causes delayed Ca(2+) influx

Cell Calcium. 2003 Apr;33(4):283-92. doi: 10.1016/s0143-4160(03)00011-3.


ATP-elicited oscillations of the concentration of free intracellular Ca(2+) ([Ca(2+)](i)) in rat brain astrocytes were abolished by simultaneous arachidonic acid (AA) addition, whereas the tetraenoic analogue 5,8,11,14-eicosatetraynoic acid (ETYA) was ineffective. Inhibition of oscillations is due to suppression by AA of intracellular Ca(2+) store refilling. Short-term application of AA, but not ETYA, blocked Ca(2+) influx, which was evoked by depletion of stores with cyclopiazonic acid (CPA) or thapsigargin (Tg). Addition of AA after ATP blocked ongoing [Ca(2+)](i) oscillations. Prolonged AA application without or with agonist could evoke a delayed [Ca(2+)](i) increase. This AA-induced [Ca(2+)](i) rise developed slowly, reached a plateau after 5 min, could be reversed by addition of bovine serum albumin (BSA), that scavenges AA, and was blocked by 1 microM Gd(3+), indicative for the influx of extracellular Ca(2+). Specificity for AA as active agent was demonstrated by ineffectiveness of C16:0, C18:0, C20:0, C18:2, and ETYA. Moreover, the action of AA was not affected by inhibitors of oxidative metabolism of AA (ibuprofen, MK886, SKF525A). Thus, AA exerted a dual effect on astrocytic [Ca(2+)](i), firstly, a rapid reduction of capacitative Ca(2+) entry thereby suppressing [Ca(2+)](i) oscillations, and secondly inducing a delayed activation of Ca(2+) entry, also sensitive to low Gd(3+) concentration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5,8,11,14-Eicosatetraynoic Acid / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Arachidonic Acid / antagonists & inhibitors
  • Arachidonic Acid / metabolism*
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Brain / cytology
  • Brain / metabolism*
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Electric Capacitance
  • Enzyme Inhibitors / pharmacology
  • Gadolinium / pharmacology
  • Indoles / pharmacology
  • Proadifen / pharmacology
  • Rats
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2Y1
  • Serum Albumin, Bovine / pharmacology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Indoles
  • P2ry1 protein, rat
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y1
  • MK-886
  • 5,8,11,14-Eicosatetraynoic Acid
  • Serum Albumin, Bovine
  • Arachidonic Acid
  • Proadifen
  • Gadolinium
  • Calcium