Comparison of the effects of different arachidonic acid metabolites on cyclic nucleotide accumulation in human peripheral lymphocytes.

The effect of PGE1, PGE2, PGD2, PGF2 alpha, PGI2, PGG2, PGA1, 12L-HETE, arachidonic acid, 15- HPETEa and linolenic acid on the accumulation of cyclic AMP in human peripheral lymphocytes was studied. PGE1, PGE2 and PGD2 were essentially equipotent as stimulators of cyclic AMP accumulation (threshold at about 10(-8)M and EC50 about 0.15 microM), PGF2 alpha was about 20 times less potent, while PGG2, 12L-HETE, 15-HPETE, PGA1 and linolenic acid were inactive. PGI2 caused a weak stimulation between 5 and 600 nM and a secondary stimulation above 3 microM. Arachidonic acid had no effect on cyclic AMP levels up to 100 microM. PGE1, PGD2, PGI2 and PGF2 alpha increased cyclic GMP in the concentrations that produced a rise in cyclic AMP, but the cyclic GMP increase was of smaller magnitude. Exogenous arachidonic acid was converted mainly to 12L-HETE, HHT and thromboxane B2 by lymphocyte suspensions. This conversion could be accounted for by contamination with blood platelets. The results show that the degree of cyclic AMP accumulation in human lymphocytes following stimulation of arachidonic acid metabolism will be critically dependent upon which prostaglandins are in fact formed by cells surrounding the lymphocytes.