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.
Karanian
J W
JW
Laboratory of Clinical Studies, National Institute Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Kim
H Y
HY
Shingu
T
T
Yergey
J A
JA
Yoffe
A
A
Salem
N
N
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001092:Arachidonate 12-Lipoxygenase / Q000097:blood; D001792:Blood Platelets / Q000502:physiology*; D004281:Docosahexaenoic Acids / Q000097:blood / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D051381:Rats
D004281:Docosahexaenoic Acids; C059528:14-hydroxydocosahexaenoic acid; C059527:11-hydroxydocosahexaenoic acid; D001092:Arachidonate 12-Lipoxygenase