Formation of hepoxilin A4, B4 and the corresponding trioxilins from 12(S)-hydroperoxy-5,8,10,14,17-icosapentaenoic acid.

12S-Hydroperoxy-5,8,10,14,17-icosapentaenoic acid (12S-HPEPE), prepared by incubating rat platelet preparations with 14C-labelled icosapentaenoic acid and purified by HPLC, was transformed into hepoxilins A4 and B4 by treatment with bovine hemin in phosphate buffer. The identity of the products, purified by HPLC as methyl esters, was confirmed by GCMS analysis of the Me tBDMSi derivatives using both El and Cl detection and of the PFB TMSi derivatives using NlCl detection. In similarity to hepoxilin A3 and B3 derived from arachidonic acid, hepoxilin A4 and B4 also possess insulin secretagogue activity. This finding contrasts with observations in the prostaglandin series where products derived from icosapentaenoic acid have been reported to possess less potent biological actions.