Arachidonic acid regulation of vasopressin release and intracellular Ca²⁺ in neurohypophysial nerve endings

The effects of arachidonic acid (AA) and arachidonic acid metabolites on vasopressin secretion and on intracellular free calcium concentration ([Ca²⁺](i)) from both intact and streptolysin-O permeabilized isolated nerve endings of the rat neurohypophysis were studied. Arachidonic acid induced a dose-dependent increase in resting vasopressin (AVP) secretion in both intact and streptolysin-O permeabilized nerve endings. Although AA also dose-dependently induced an increase in [Ca²⁺](i) in 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 vasopressin release. The potentiation of secretion occurred despite an AA-induced reduction in K⁺-evoked Ca²⁺ influx. In addition, AA reinitiated secretion following a decline in the Ca²⁺-dependent exocytotic secretory response suggesting a separate secretory mechanism from Ca²⁺-induced secretion. Inhibition of the metabolic pathways for AA suggested that AA itself mediates the secretory effects and that AA is likely subject to rapid metabolism by lipoxygenases.