PACAP Increases the Cytosolic Ca2−/Concentration and Stimulates Somatodendritic Vasopresson Release in Rat Supraoptic Neurons

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Abstract
Pituitary adenylate cyclase activating polypeptide (PACAP)‐like immunoreactivity and its receptor mRNA have been reported in the supraoptic and the paraventricular nucleus (SON and PVN, respectively) and PACAP has been implicated in the regulation of magnocellular neurosecretory cell function. To examine the site and the mechanism of the action of PACAP in the neurosecretory cells, we measured AVP release from SON slice preparations and the cytosolic Ca2+concentration ([Ca2+]i) from single dissociated SON neurons. PACAP at concentrations from 10−12to 10−7M increased [Ca2+]iin dissociated SON neurons in a dose‐dependent manner. The patterns of the PACAP‐induced [Ca2+]iincrease were either sustained increase or cytosolic Ca2+oscillations. PACAP (10−7M) increased [Ca2+]iin 27 of 27 neurons and glutamate (10−4M) increased [Ca2+]iin 19 of 19 SON neurons examined, whereas angiotensin II (10−7M) increased [Ca2+]iin only 15 of 60 SON neurons examined. PACAP at lower concentrations (10−10to 10−8M) increased [Ca2+]iin 70–80% of neurons examined. Although the onset and recovery of the PACAP‐induced [Ca2+]iincrease were slower than those observed with glutamate, the spatial distribution of the [Ca2+]iincreases in response to the two ligands were similar: [Ca2+]iincrease at the proximal dendrites was larger and faster and that at the center of the soma was smaller and slower. The PACAP‐induced [Ca2+]iresponseswere abolished by extracellular Ca2+removal, thel‐type Ca2+‐channel blocker, nicardipine, or by replacement of extracellular Na+with N‐methyld‐glucamine, and were partially inhibited by the Na+‐channel blocker, tetrodotoxin. The N‐type Ca2+‐channel blocker,ω‐conotoxin GVIA did not significantly inhibit the PACAP‐induced [Ca2+]iresponses. Furthermore, PACAP (10−7M) as well as glutamate (10−4M) increased AVP release from SON slice preparations, and extracellular Ca2+removal or nicardipine inhibited the AVP release in response to PACAP.These results indicate that PACAP enhances Ca2+entry via voltage‐gated Ca2+channels and increases [Ca2+]i, which, in turn, stimulates somatodendritic vasopressin release by directly activating PACAP receptors on SON neurons. The results also suggest that PACAP in the SON may play a pivotal role in the control of the neurohypophyseal function at the level of the soma or the dendrites.

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