Chlorpromazine-induced inhibition of catecholamine secretion by a differential blockade of nicotinic receptors and L-type Ca2+ channels in rat pheochromocytoma cells
SCIE
SCOPUS
- Title
- Chlorpromazine-induced inhibition of catecholamine secretion by a differential blockade of nicotinic receptors and L-type Ca2+ channels in rat pheochromocytoma cells
- Authors
- Lee, IS; Park, TJ; Suh, BC; Kim, YS; Rhee, IJ; Kim, KT
- Date Issued
- 1999-09-15
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Abstract
- We investigated the effect of chlorpromazine (CPZ), a phenothiazine neuroleptic, on catecholamine secretion in rat pheochromocytoma (PC12) cells. CPZ inhibited [H-3]norepinephrine ([H-3]NE) secretion induced by 1,1 dimethyl-4-phenylpiperazinium iodide (DMPP), an agonist of nicotinic acetylcholine receptors (nAChRs) with an IC50 value of 1.0 +/- 0.2 mu M. The DMPP-induced rise in cytosolic free Ca2+ concentration [Ca2+], was inhibited by CPZ with an IC50 of 1.9 +/- 0.1 mu M. The DMPP induced increase in cytosolic free Nat concentration [Na+], was also inhibited by CPZ with a similar potency. Furthermore, the binding of [H-3]nicotine to PC12 cells was inhibited by CPZ with an IC50 value of 2.7 +/- 0.6 mu M, suggesting that the nAChRs themselves are inhibited by CPZ. In addition, both 70 mM K+-induced [H-3]NE secretion and [Ca2+](i) increase were inhibited by CPZ with IC50 of 7.9 +/- 1.1 and 6.2 +/- 0.3 mu M, respectively. Experiments with Ca2+ channel antagonists suggest that L-type Ca2+ channels are mainly responsible for the inhibition. We conclude that CPZ inhibits catecholamine secretion by blocking nAChRs and L-type Ca2+ channels, with the former being more sensitive to CPZ. (C) 1999 Elsevier Science Inc.
- Keywords
- chlorpromazine; catecholamine secretion; nicotinic receptor; L-type Ca2+ channels; PC12 cells; SENSITIVE CALCIUM CHANNELS; ADRENAL CHROMAFFIN CELLS; PC12 CELLS; ACETYLCHOLINE-RECEPTOR; H-3 CHLORPROMAZINE; POTASSIUM CURRENTS; BINDING-SITES; RELEASE; SODIUM; DRUGS
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/20310
- DOI
- 10.1016/S0006-2952(99)00181-1
- ISSN
- 0006-2952
- Article Type
- Article
- Citation
- BIOCHEMICAL PHARMACOLOGY, vol. 58, no. 6, page. 1017 - 1024, 1999-09-15
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- There are no files associated with this item.
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