Park T, Bae S, Choi S, Kang B, Kim K
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, 31, Pohang 790-784, San, South Korea.
Biochem Pharmacol. 2001 Apr 15;61(8):1011-9. doi: 10.1016/s0006-2952(01)00577-9.
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. [(3)H]Norepinephrine ([(3)H]NE) secretion induced by activation of nAChRs was inhibited by clozapine and CPZ with half-maximal inhibitory concentrations (IC(50)) of 10.4 +/- 1.1 and 3.9 +/- 0.2 microM, 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, [(3)H]nicotine binding to chromaffin cells was inhibited by clozapine and CPZ with IC(50) values of approximately 19 and 2 microM, respectively. On the other hand, [(3)H]NE secretion induced by high K(+) was inhibited by clozapine and CPZ with similar IC(50) values of 15.5 +/- 3.8 and 17.1 +/- 3.9 microM, 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.
在牛肾上腺嗜铬细胞中，研究了氯氮平对烟碱型乙酰胆碱受体（nAChRs）和电压敏感性钙通道（VSCCs）活性的影响，并与氯丙嗪（CPZ）进行了比较。nAChRs激活诱导的[（3）H]去甲肾上腺素（[（3）H]NE）分泌受到氯氮平和CPZ的抑制，其半数最大抑制浓度（IC（50））分别为10.4±1.1和3.9±0.2微摩尔。烟碱刺激诱导的细胞内钙增加和细胞外无钙时的内向电流也受到氯氮平和CPZ的抑制，但CPZ的抑制作用更强。此外，氯氮平和CPZ对嗜铬细胞的[（3）H]尼古丁结合均有抑制作用，IC（50）值分别约为19和2微摩尔。另一方面，高钾诱导的[（3）H]NE分泌受到氯氮平和CPZ的抑制，IC（50）值相似，分别为15.5±3.8和17.1±3.9微摩尔。我们的结果表明，氯氮平和CPZ一样，抑制nAChRs和VSCCs，从而导致儿茶酚胺分泌受到抑制，并且氯氮平在抑制nAChRs方面的效力远低于CPZ。
