Premium
Arachidonic acid and docosahexaenoic acid suppress thrombin‐evoked Ca 2+ response in rat astrocytes by endogenous arachidonic acid liberation
Author(s) -
Sergeeva Marina,
Strokin Mikhail,
Wang Hong,
Ubl Joachim J.,
Reiser Georg
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01052.x
Subject(s) - arachidonic acid , docosahexaenoic acid , eicosapentaenoic acid , phospholipase a2 , endogeny , thrombin , polyunsaturated fatty acid , biochemistry , agonist , phospholipase , extracellular , intracellular , phospholipase c , chemistry , endocrinology , biology , medicine , fatty acid , receptor , enzyme , platelet , immunology
Arachidonic (AA) and docosahexaenoic acid (DHA) are the major polyunsaturated fatty acids (PUFAs) in the brain. However, their influence on intracellular Ca 2+ signalling is still widely unknown. In astrocytes, the amplitude of thrombin‐ induced Ca 2+ response was time‐dependently diminished by AA and DHA, or by the AA tetraynoic analogue ETYA, but not by eicosapentaenoic acid (EPA). Thrombin‐elicited Ca 2+ response was reduced (20–30%) by 1‐min exposure to AA or DHA. Additionally, 1‐min application of AA or DHA together with thrombin in Ca 2+ ‐free medium blocked Ca 2+ influx, which followed after readdition of extracellular Ca 2+ . EPA and ETYA, however, were ineffective. Long‐term treatment of astrocytes with AA and DHA, but not EPA reduced the amplitude of the thrombin‐induced Ca 2+ response by up to 80%. AA and DHA caused a comparable decrease in intracellular Ca 2+ store content. Only DHA and AA, but not EPA or ETYA, caused liberation of endogenous AA by cytosolic phospholipase A2 (cPLA2). Therefore, we reasoned that the suppression of Ca 2+ response to thrombin by AA and DHA could be due to release of endogenous AA. Possible participation of AA metabolites, however, was excluded by the finding that specific inhibitors of the different oxidative metabolic pathways of AA were not able to abrogate the inhibitory AA effect. In addition, thrombin evoked AA release via activation of cPLA2. From our data we propose a novel model of positive/negative‐feed‐back in which agonist‐induced release of AA from membrane phospholipids promotes further AA release and then suppresses agonist‐induced Ca 2+ responses.