Smooth muscle effects of hydroxylated docosahexaenoates produced from human platelet

Washed platelets (10(8)cells/ml) are capable of metabolizing docosahexaenoic acid (22:6w3, DHE) to 12-lipoxygenase derivatives. The two major metabolites of the DHE thus formed were collected and derivatized for analysis by GC/MS/EI. The structures assigned were 14(S) and 11(S) hydroxy-docosahexenoate (HDHE). 12-lipoxygenase inhibitors such as ETYA inhibited the production of HDHE. The metabolites formed are biologically active as they are capable of inducing a weak contraction in airway but not vascular smooth muscle preparations; a thromboxane-agonist (U46619) was 10 to 20-fold more efficacious than HDHE in the guinea pig lung parenchymal strip. HDHE may act in part through stimulation of leukotriene production as increased peptidyl-leukotriene levels were associated with the HDHE-induced contraction in this preparation and a lipoxygenase inhibitor (NDGA) was capable of a partial blockade of this response. In addition, HDHE antagonizes the contractile effects of the thromboxane-agonist, U46619, especially in vascular smooth muscle. Stimulation of the sulfidopeptido leukotrienes and thromboxane antagonism may therefore be important aspects of the biological function of HDHE.