Formation and action of 8-hydroxy-11,12-epoxy-5,9,14-icosatrienoic acid in Aplysia: a possible second messenger in neurons.

In Aplysia neural tissue, the release and metabolism of arachidonic acid are stimulated by histamine or by activation of the identified L32 nerve cell circuit of the abdominal ganglion. Previously we found that histamine and intracellular stimulation of L32 cells, which are putatively histaminergic neurons, cause the production of 12-hydroxy-5,8,10,14-icosatetraenoic acid (12-HETE), a product of the 12-lipoxygenase pathway formed through 12-hydroperoxy-5,8,10,14-icosatetraenoic acid (12-HPETE). 12-HPETE, but not 12(S)-HETE, mimics the dual-action response of L14 ink motor neurons to histamine and stimulation of L32. 12-HPETE can also be further metabolized to 8-hydroxy-11,12-epoxy-5,9,14-icosatrienoic acid (8-HEpETE) which was identified by HPLC, enzymatic hydrolysis, and GC/MS. Production of 8-HEpETE is specific, as its positional isomer 10-hydroxy-11,12-epoxy-5,8,14-icosatrienoic acid is not formed after physiologic stimulation. 8-HEpETE can elicit the late component (hyperpolarization) of the dual-action response in L14 cells, suggesting that it may be a second messenger in Aplysia.