Effect of colchicine and ATP deprivation on release of arachidonic acid from platelets exposed to thrombin or ionophore A 23187: Susan Rittenhouse-Simmons, Daniel Deykin, Boston University, Boston VA Hospital, Boston, Massachusetts

Abstract

It has been reported that the prostaglandin (PG) precursor, arachidonic acid, produces divergnet hemodynamic responses in the feline pulmonary vascular bed. However, the pattern of arachidonic acid products formed in the lung of this species is unknown. In order to determine the type and activity of terminal enzymes in the lung, prostaglandin biosynthesis by microsomes from cat lung was studied using the prostaglandin endoperoxide, PHG2, as a substrate. The major products of incubations of PGH2 with mcirosomes were thromboxane (TX) B2 (the major metabolite of TXA2), 6-keto-PGF1α (the breakdown product of PGI2) and 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT). Formation of TXB2 was markedly reduced by imidazole. Tranylcypromine decreased the formation of TXB2 and HHT and inhibited the formation of 6-keto-PGF1α. At low PGH2 concentrations, equal production of TXB2 and 6-keto-PGF1α was observed. However, as PGH2 concentration increased, 6-keto-PGF1α production approached early saturation while TXB2 production increased in a linear fashion. These results suggest that enzymatic formation of TXA2 and PGI2 is a function of substrate availability in the lung. These findings provide a possible explanation for the divergent hemodynamic responses to arachidonic acid infusions at high and low concentrations in the feline pulmonary vascular bed.