ARACHIDONIC-ACID INHIBITS THE RECEPTOR-ST IMULATED INCREASE IN INTRACELLULAR CA2-INDEPENDENT AND CAMP-INDEPENDENT MECHANISMS( CONCENTRATIONVIA RECEPTOR)

Arachidonic acid (AA), among with the other fatty acids, at concentrat ions of 1-100 muM can increase the basal cytosolic Ca2+ level ([Ca2+]i ) in platelets, neutriphils, Ehrlich ascite tumor cells (EATC), myocyt es, etc. On the other hand it is known that AA (at the same concentrat ions) inhibits the [Ca2+]i elevation induced by some agents in pituita ry GH3-Cells but practically does not affect the basal Ca2+-level. We have shown that AA at 0.1-1 muM concentration-dependently inhibits the [Ca2+]i increase in rat thymocytes (up to a complete inhibition at 1 muM AA) stimulated by- 1-20 mug/ml Con A or by 10 nM ionomycin or by 1 muM reticular Ca2+-ATPase blocker 2,5-di-(tert-butyl)-1,4-benzohydroq uinon (BHQ). The product of a cyclooxygenase AA metabolism PGE1 also i nhibits the Con A-induced elevation of [Ca2+]i. However, at concentrat ion of 100-fold higher than the effective concentration of AA PGE1 inh ibits only about 50% of Ca2+-response to Con A. The effect of PGE1 was identical to the action of dibutiril-cAMP and forskolin but was not a dditive to the effects of these reagents. The effect of AA was additiv e to those of PGE1, dibutiril-cAMP or forskolin. This fact indicates t hat the mechanism of AA inhibitory action is cAMP-independent. AA inhi bited the receptor-stimulated [Ca2+]i elevation in the Ehrlich ascites tumor cells. In these cells the initial [Ca2+]i increase was shown to be due to Ca2+ mobilization from intracellular stores, while in thymo cytes the [Ca2+]i-response arises primarily from an increased Ca2+ inf lux. To sum up, the results obtained support the assumption that in th ymocytes AA inhibits both IP3-dependent Ca2+ efflux from intracellular pools and Ca2+ entry from the external medium through the Ca2+-channe ls of the plasma membrane. The latter are likely to be the Ca2+-activa ted Ca2+-channels rather than the receptor-operated ones.