Arachidonic acid in astrocytes blocks Ca2+ oscillations by inhibiting store-operated Ca2+ entry, and causes delayed Ca2+ influx

ATP-elicited oscillations of the concentration of free intracellular Ca2+ ([Ca2+](i)) in rat brain astrocytes were abolished by simultaneous arachidonic acid (AA) addition, whereas the tetraenoic analogue 5,8,11,14-cicosatetraynoic acid (ETYA) was ineffective. Inhibition of oscillations is due to suppression by AA of intracellular Ca2+ store refilling. Short-term application of AA, but not ETYA, blocked Ca2+ influx, which was evoked by depletion of stores with cyclopiazonic acid (CPA) or thapsigargin (Tg). Addition of AA after ATP blocked ongoing [Ca2+](i) oscillations. Prolonged AA application without or with agonist could evoke a delayed [Ca2+](i) increase. This AA-induced [Ca2+](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 muM Gd3+, indicative for the influx of extracellular Ca2+. 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 [Ca2+](i),, firstly, a rapid reduction of capacitative Ca2+ entry thereby suppressing [Ca2+](i) oscillations, and secondly inducing a delayed activation of Ca2+ entry, also sensitive to low Gd3+ concentration. (C) 2003 Elsevier Science Ltd. All rights reserved.