Arachidonic acid in astrocytes blocks Ca(2+) oscillations by inhibiting store-operated Ca(2+) entry, and causes delayed Ca(2+) influx.
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.
Sergeeva
Marina
M
Institut für Neurobiochemie, Medizinische Fakultät der Otto-von-Guericke-Universität Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
Strokin
Mikhail
M
Wang
Hong
H
Ubl
Joachim J
JJ
Reiser
Georg
G
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D025802:Electric Capacitance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D002722:Chlorobenzenes
D015117:5,8,11,14-Eicosatetraynoic Acid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016718:Arachidonic Acid; D002118:Calcium; D004791:Enzyme Inhibitors; D005682:Gadolinium; D007211:Indoles; D011335:Proadifen; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D012710:Serum Albumin, Bovine; C546384:P2ry1 protein, rat; C060893:MK-886; D002722:Chlorobenzenes