Arachidonic acid abolishes the mitogen-induced increase in cytosolic free Ca2+ and intracellular pHi in rat thymocytes.
The effects of arachidonic acid (AA) and the lectin mitogens, concanavalin A (Con A) and phytohemagglutinin (PHA), on [Ca2+]i and pHi in rat thymocytes have been studied by using the intracellular fluorescent probes, Fura-2 and BCECF. It was revealed that exogenous AA (3 microM), in addition to the well-known changes in basal [Ca2+]i and pHi, also caused a complete blockade of [Ca2+]i and pHi signals induced by Con A (10 micrograms/ml) and PHA (10 micrograms/ml). In contrast, exposure of thymocytes to mitogens did not prevent the AA-induced increase in [Ca2+]i and decrease in pHi. In experiments with sodium propionate, the similarity between AA action and EIPA (ethylisopropylamiloride), an inhibitor of Na+/H+ exchangers, was revealed. It is proposed that the inhibitory effect of AA on mitogen-induced lymphocyte proliferation is due primarily to the blockade of transmembrane [Ca2+]i and pHi signals, associated with a sustained cytosolic acidification.
Astashkin
E I
EI
Scientific Production Association Biotechnology, Moscow, Russian Federation.
Khodorova
A B
AB
Surin
A M
AM
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D016257:Fura-2; D006863:Hydrogen-Ion Concentration; D008934:Mitogens / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism*
D005452:Fluoresceins; D005456:Fluorescent Dyes; D008934:Mitogens; D010835:Phytohemagglutinins; D003208:Concanavalin A; D016718:Arachidonic Acid; D000584:Amiloride; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D002118:Calcium; D016257:Fura-2; C039614:ethylisopropylamiloride