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Inhibition of nicotinic acetylcholine receptors and calcium channels by clozapine in bovine adrenal chromaffin cells.

Cited 25 time in Web of Science Cited 26 time in Scopus
Issue Date
2001-04
Publisher
Elsevier
Citation
Biochemical Pharmacology 2001;61:1011-1019
Keywords
ClozapineChlorpromazineNicotinic acetylcholine receptorsCatecholamine secretionChromaffin cells
Abstract
The effects of clozapine on the activities of nicotinic acetylcholine receptors (nAChRs) and voltage-sensitive calcium channels (VSCCs) were investigated and compared with those of chlorpromazine (CPZ) in bovine adrenal chromaffin cells. [3H]Norepinephrine ([3H]NE) secretion induced by activation of nAChRs was inhibited by clozapine and CPZ with half-maximal inhibitory concentrations ( 50) of 10.4 ± 1.1 and 3.9 ± 0.2 μM, respectively. Both cytosolic calcium increase and inward current in the absence of extracellular calcium induced by nicotinic stimulation were also inhibited by clozapine and CPZ, but the greater inhibition was achieved by CPZ. In addition, [3H]nicotine binding to chromaffin cells was inhibited by clozapine and CPZ with 50 values of approximately 19 and 2 μM, respectively. On the other hand, [3H]NE secretion induced by high K+ was inhibited by clozapine and CPZ with similar 50 values of 15.5 ± 3.8 and 17.1 ± 3.9 μM, respectively. Our results suggest that clozapine, as well as CPZ, inhibits nAChRs and VSCCs, thereby causing inhibition of catecholamine secretion, and that clozapine is much less potent than CPZ in inhibiting nAChRs.
ISSN
0006-2952
Language
English
URI
https://hdl.handle.net/10371/68889
DOI
https://doi.org/10.1016/S0006-2952(01)00577-9
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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