Ca2+o-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 [14C]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 microM) 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 [14C]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 [14C]choline. With the same treatment vesamicol only slightly affected the release of endogenous ACh. Under the same conditions the Ca2(+)-independent [14C]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.
Adam-Vizi
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V
2nd Institute of Biochemistry, Semmelweis University of Medicine, Budapest, Hungary.
Deri
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Z
Vizi
E S
ES
Sershen
H
H
Lajtha
A
A
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014701:Veratridine / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D010880:Piperidines; C006189:vesamicol; D014701:Veratridine; D000109:Acetylcholine; D002118:Calcium