EFFECT OF IN-VITRO INCORPORATION OF PROSTANOID PRECURSORS, SUPEROXIDERADICAL AND HYDROGEN-PEROXIDE ON PLATELET-FUNCTION

The level of cyclic adenosine monophosphate (cAMP) in human platelets is known to be an important regulator of platelet function. The polyun saturated fatty acids (PUFA) dihomo-gamma-linolenic acid (DHLA), and e icosapentaenoic acid (EPA), precursors of the prostaglandin (PG) 1 and 3 series respectively, were studied for their ability to stimulate pl atelet cAMP and/or PGE(1) levels, and to inhibit platelet aggregation (PAg). Incubation of washed platelets (1 x 10(8)/ml) with 125 mu M DHL A increased intraplatelet levels of PGE(1) from 197+/-7 to 1622+/-9.7 picograms/10(8), cAMP from 3+/-0.8 to 31+/-1.9 picomoles/10(8), and in hibited collagen-induced PAg. Addition of 1 mu mole of xanthine per un it of xanthine oxidase (a superoxide radical generating system) to the incubating medium potentiated the effects of both fatty acids, wherea s 240 mu M Hydrogen Peroxide (H2O2) inhibited these effects. These res ults suggest that: (1) DHLA may be more effective in inhibiting PAg th an EPA, which has been reported to reduce the incidence of coronary di seases in some human populations; (2) That superoxide radical may acti vate the platelet cyclooxygenase system to increase lipid peroxidation of these PUFA prostanoid precursors and may result in the inhibition of PAg, whereas H2O2 may have an opposite effect.