ARACHIDONIC-ACID REGULATION OF VASOPRESSIN RELEASE AND INTRACELLULAR CA2-ENDINGS( IN NEUROHYPOPHYSEAL NERVE)

The effects of arachidonic acid (AA) and arachidonic acid metabolites on vasopressin secretion and on intracellular free calcium concentrati on ([Ca2+](i)) from both intact and streptolysin-O permeabilized isola ted nerve endings of the rat neurohypophysis were studied. Arachidonic acid induced a dose-dependent increase in resting vasopressin (AVP) s ecretion in both intact and streptolysin-O permeabilized nerve endings . Although AA also dose-dependently induced an increase in [Ca2+](i) i n intact nerve endings, the AA-induced secretory response was largely independent of an increase in [Ca2+](i). Secretory responses in intact nerve endings showed AA-induced secretion to be sustained and that AA -induced vasopressin secretion occurs via exocytosis. Arachidonic acid also dose-dependently potentiated K+-depolarization evoked vasopressi n release. The potentiation of secretion occurred despite an AA-induce d reduction in K+-evoked Ca2+ influx. In addition, AA reinitiated secr etion following a decline in the Ca2+-dependent exocytotic secretory r esponse suggesting a separate secretory mechanism from Ca2+-induced se cretion. Inhibition of the metabolic pathways for AA suggested that AA itself mediates the secretory effects and that AA is likely subject t o rapid metabolism by lipoxygenases.