Recently, we have measured in erythrocytes a voltage-modulated and dihydropyridine-inhibited calcium influx. Since arachidonic acid and other polyunsaturated fatty acids influence the activities of most ion channels, we studied their effects on the erythrocyte Ca2+ influx. It was measured on fresh erythrocytes, isolated from healthy donors, using the fluorescent dye Fura 2 as indicator of [Ca2+](i). AA (5-50 muM) and EPA (20-30 muM) stimulated a concentration-dependent increase in [Ca2+](i), deriving from extracellular calcium (1 mM), without affecting the intra- and extracellular pH and membrane voltage. The Ca2+ influx rate varied from 0.5 to 3 nM Ca2+/s in the presence of AA and from 0.9 to 1.7 nM Ca2+/s with EPA. The Ca2+ influx elicited by AA and EPA was not inhibited by dihydropyridines, while cyclooxygenase inhibitors were effective and PGE1 or PGE2 did not produce any effect. We conclude that AA could activate an erythrocyte voltage-independent Ca2+ transport via an intermediate product of cyclooxygenase pathway; however, a direct interaction with the membrane lipid-protein cannot be excluded. (C) 2002 Elsevier Science (USA). All rights reserved.