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Arachidonic acid (AA) is oxidized via three pathways which result in several series of distinct metabolites. Cyclooxygenase produces prostaglandins (PGs), prostacyclins, and thromboxanes. Lipoxygenase produces hydroperoxy/hydroxyeicosatetraenoic acids (HPETE/HETEs) and leukotrienes. Epoxygenase, a recently uncovered pathway, results in epoxyeicosatrienoic acids (EETs). Based on reverse phase HPLC product analysis, this study establishes that all three pathways of AA metabolism are present in microsomal incubates of the neural lobe of the pituitary gland. Addition of PGE2 to incubated fragments of neural lobes of the rat pituitary stimulates secretion of both arginine vasopressin (AVP) and oxytocin in vitro. Inclusion of 5-HETE and 12-HETE in the incubation medium stimulates marginal release of AVP and oxytocin by 12-HETE only. The magnitude of AVP and oxytocin secretion stimulated by the epoxygenase metabolites 8,9-, 11,12-, and 14,15-EET is equal to that caused by PGE2. Maximal stimulation of secretion (3- to 4-fold) requires an EET concentration 10-15 times greater than that of PGE2. In contrast, 5,6-EET is inactive. These data suggest that oxygenated products of AA play a role in AVP and oxytocin secretion. Although PGs appear to be the dominant arachidonate metabolites involved in the release of AVP and oxytocin, the EETs probably have a contributing role.
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