Tj. Park et al., Inhibition of nicotinic acetylcholine receptors and calcium channels by clozapine in bovine adrenal chromaffin cells, BIOCH PHARM, 61(8), 2001, pp. 1011-1019
The effects of clozapine on the activities of nicotinic acetylcholine recep
tors (nAChRs) and voltage-sensitive calcium channels (VSCCs) were investiga
ted and compared with those of chlorpromazine (CPZ) in bovine adrenal chrom
affin cells. [H-3]Norepinephrine ([H-3]NE) secretion induced by activation
of nAChRs was inhibited by clozapine and CPZ with half-maximal inhibitory c
oncentrations (IC50) of 10.4 +/- 1.1 and 3.9. +/- 0.2 muM, respectively. Bo
th cytosolic calcium increase and inward current in the absence of extracel
lular calcium induced by nicotinic stimulation were also inhibited by cloza
pine and CPZ, but the greater inhibition was achieved by CPZ. In addition,
[H-3]nicotine binding to chromaffin cells was inhibited by clozapine and CP
Z with IC50 values of approximately 19 and 2 muM, respectively. On the othe
r hand, [H-3]NE secretion induced by high K+ was inhibited by clozapine and
CPZ with similar IC50 values of 15.5 +/- 3.8 and 17.1 +/- 3.9 muM, respect
ively. 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. (C) 2001 Elsev
ier Science Inc. All rights reserved.