CA-2+(0)-INDEPENDENT VERATRIDINE-EVOKED ACETYLCHOLINE-RELEASE FROM STRIATAL SLICES IS NOT INHIBITED BY VESAMICOL (AH5183) - MOBILIZATION OF DISTINCT TRANSMITTER POOLS

The effect of 2-(4-phenylpiperidino)cyclohexanol (AH5183 or vesamicol), a compound known to block the uptake of acetylcholine (ACh) into cholinergic synaptic vesicles, on the release of endogenous and ]C-14[ACh from slices of rat striatum was investigated. ACh release was evoked either by electrical stimulation or by veratridine. The effect of electrical stimulation was entirely dependent on external Ca2+. By contrast, veratridine (40 mu-M) also enhanced ACh release in the absence of Ca2+. Indeed, with veratridine two components were clearly distinguished: one dependent on external Ca2+ and the other not. Vesamicol inhibited [C-14]ACh release evoked by both veratridine and electrical stimulation in the presence of external Ca2+, provided it was added to the tissue prior to loading with [C-14]choline. With the same treatment vesamicol only slightly affected the release of endogenous ACh. Under the same conditions the Ca2+-independent [C-14]ACh release evoked by veratridine was not prevented by vesamicol. The differential responsiveness to vesamicol suggests that ACh pools involved in Ca2+(o)-dependent ACh release are different from those mobilized during Ca2+(o)-independent ACh release.