Arachidonic acid inhibits capacitative calcium entry in rat thymocytes and human neutrophils.
Emptying the intracellular Ca2+ stores by treatment with the endomembrane Ca2+-ATPase inhibitor thapsigargin activates capacitative Ca2+ entry (CCE). This can be evidenced in fura-2-loaded cells by an increase of [Ca2+]i or by an acceleration of Mn2+ entry. Micromolar concentrations of arachidonic acid inhibited CCE induced by treatment with thapsigargin in rat thymocytes and in human neutrophils. This inhibitory action was shared by other unsaturated fatty acids, but not by the saturated arachidic acid nor by arachidonic acid methyl ester. The effect was not due to metabolites derived from arachidonic acid since several non-metabolizable analogs were able to reproduce it. Phorbol dibutyrate (PDB) acted similarly, suggesting that the inhibitory effect could be mediated by activation of protein kinase C (PKC). However, whereas the inhibition of CCE by PDB was reversed by treatment with the PKC inhibitor staurosporin, the inhibition by arachidonic acid was not. We find that unsaturated fatty acids antagonized microsomal dealkylation of benzyl-resorufin, a cytochrome P450-mediated activity, with the same specificity profile as for inhibition of CCE. These results are consistent with previous proposals suggesting that a microsomal cytochrome P450 may be involved in the regulation of CCE.
Alonso-Torre
S R
SR
Departamento de Fisiología y Bioquímica, Instituto de Biología y Genética Molecular, Universidad de Valladolid y CSIC, Facultad de Medicina, Spain.
García-Sancho
J
J
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004553:Electric Conductivity; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D015240:Phorbol 12,13-Dibutyrate; D003577:Cytochrome P-450 Enzyme System; C077445:7-benzoxyresorufin-O-dealkylase; D010088:Oxidoreductases; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium