Chlorpromazine-induced inhibition of catecholamine secretion by a differential blockade of nicotinic receptors and L-type Ca2+ channels in rat pheochromocytoma cells

Ihn Soon Lee; Tae Ju Park; Byung Chang Suh; Yong Sik Kim; In Ja Rhee; Kyong Tai Kim

doi:10.1016/S0006-2952(99)00181-1

Chlorpromazine-induced inhibition of catecholamine secretion by a differential blockade of nicotinic receptors and L-type Ca²⁺ channels in rat pheochromocytoma cells

Ihn Soon Lee, Tae Ju Park, Byung Chang Suh, Yong Sik Kim, In Ja Rhee, Kyong Tai Kim

Department of Brain Sciences

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

We investigated the effect of chlorpromazine (CPZ), a phenothiazine neuroleptic, on catecholamine secretion in rat pheochromocytoma (PC12) cells. CPZ inhibited [³H]norepinephrine ([³H]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 μM. The DMPP-induced rise in cytosolic free Ca²⁺ concentration [Ca²⁺](i) was inhibited by CPZ with an IC₅₀ of 1.9 ± 0.1 μM. The DMPP-induced increase in cytosolic free Na⁺ concentration [Na⁺](i) was also inhibited by CPZ with a similar potency. Furthermore, the binding of [³H]nicotine to PC12 cells was inhibited by CPZ with an IC₅₀ value of 2.7 ± 0.6 μM, suggesting that the nAChRs themselves are inhibited by CPZ. In addition, both 70 mM K⁺-induced [³H]NE secretion and [Ca²⁺](i) increase were inhibited by CPZ with IC₅₀ of 7.9 ± 1.1 and 6.2 ± 0.3 μM, 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. Copyright (C) 1999 Elsevier Science Inc.

Original language	English
Pages (from-to)	1017-1024
Number of pages	8
Journal	Biochemical Pharmacology
Volume	58
Issue number	6
DOIs	https://doi.org/10.1016/S0006-2952(99)00181-1
State	Published - 15 Sep 1999

Bibliographical note

Funding Information:
We wish to thank Ms. S. K. Song for the measurement of inositol 1,4,5-trisphosphate and Ms. G. Hoschek for editing the manuscript. This research was supported by the Korea Ministry of Science and Technology under the Brain Science Research Program. We also wish to acknowledge the financial support of the Ministry of Health and Welfare and the Korea Research Foundation (program year 1998) and the Basic Science Research Institute Program (BSRI-98-4435) from the Ministry of Education.

Keywords

Catecholamine secretion
Chlorpromazine
L-type Ca channels
Nicotinic receptor
PC12 cells

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10.1016/S0006-2952(99)00181-1

Cite this

@article{b5fe1a1c8a414e99b9a72709462fdefa,

title = "Chlorpromazine-induced inhibition of catecholamine secretion by a differential blockade of nicotinic receptors and L-type Ca2+ channels in rat pheochromocytoma cells",

abstract = "We investigated the effect of chlorpromazine (CPZ), a phenothiazine neuroleptic, on catecholamine secretion in rat pheochromocytoma (PC12) cells. CPZ inhibited [3H]norepinephrine ([3H]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 μM. The DMPP-induced rise in cytosolic free Ca2+ concentration [Ca2+](i) was inhibited by CPZ with an IC50 of 1.9 ± 0.1 μM. The DMPP-induced increase in cytosolic free Na+ concentration [Na+](i) was also inhibited by CPZ with a similar potency. Furthermore, the binding of [3H]nicotine to PC12 cells was inhibited by CPZ with an IC50 value of 2.7 ± 0.6 μM, suggesting that the nAChRs themselves are inhibited by CPZ. In addition, both 70 mM K+-induced [3H]NE secretion and [Ca2+](i) increase were inhibited by CPZ with IC50 of 7.9 ± 1.1 and 6.2 ± 0.3 μM, 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. Copyright (C) 1999 Elsevier Science Inc.",

keywords = "Catecholamine secretion, Chlorpromazine, L-type Ca channels, Nicotinic receptor, PC12 cells",

author = "Lee, {Ihn Soon} and Park, {Tae Ju} and Suh, {Byung Chang} and Kim, {Yong Sik} and Rhee, {In Ja} and Kim, {Kyong Tai}",

note = "Funding Information: We wish to thank Ms. S. K. Song for the measurement of inositol 1,4,5-trisphosphate and Ms. G. Hoschek for editing the manuscript. This research was supported by the Korea Ministry of Science and Technology under the Brain Science Research Program. We also wish to acknowledge the financial support of the Ministry of Health and Welfare and the Korea Research Foundation (program year 1998) and the Basic Science Research Institute Program (BSRI-98-4435) from the Ministry of Education.",

year = "1999",

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volume = "58",

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T1 - Chlorpromazine-induced inhibition of catecholamine secretion by a differential blockade of nicotinic receptors and L-type Ca2+ channels in rat pheochromocytoma cells

AU - Lee, Ihn Soon

AU - Park, Tae Ju

AU - Suh, Byung Chang

AU - Kim, Yong Sik

AU - Rhee, In Ja

AU - Kim, Kyong Tai

N1 - Funding Information: We wish to thank Ms. S. K. Song for the measurement of inositol 1,4,5-trisphosphate and Ms. G. Hoschek for editing the manuscript. This research was supported by the Korea Ministry of Science and Technology under the Brain Science Research Program. We also wish to acknowledge the financial support of the Ministry of Health and Welfare and the Korea Research Foundation (program year 1998) and the Basic Science Research Institute Program (BSRI-98-4435) from the Ministry of Education.

PY - 1999/9/15

Y1 - 1999/9/15

N2 - We investigated the effect of chlorpromazine (CPZ), a phenothiazine neuroleptic, on catecholamine secretion in rat pheochromocytoma (PC12) cells. CPZ inhibited [3H]norepinephrine ([3H]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 μM. The DMPP-induced rise in cytosolic free Ca2+ concentration [Ca2+](i) was inhibited by CPZ with an IC50 of 1.9 ± 0.1 μM. The DMPP-induced increase in cytosolic free Na+ concentration [Na+](i) was also inhibited by CPZ with a similar potency. Furthermore, the binding of [3H]nicotine to PC12 cells was inhibited by CPZ with an IC50 value of 2.7 ± 0.6 μM, suggesting that the nAChRs themselves are inhibited by CPZ. In addition, both 70 mM K+-induced [3H]NE secretion and [Ca2+](i) increase were inhibited by CPZ with IC50 of 7.9 ± 1.1 and 6.2 ± 0.3 μM, 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. Copyright (C) 1999 Elsevier Science Inc.

AB - We investigated the effect of chlorpromazine (CPZ), a phenothiazine neuroleptic, on catecholamine secretion in rat pheochromocytoma (PC12) cells. CPZ inhibited [3H]norepinephrine ([3H]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 μM. The DMPP-induced rise in cytosolic free Ca2+ concentration [Ca2+](i) was inhibited by CPZ with an IC50 of 1.9 ± 0.1 μM. The DMPP-induced increase in cytosolic free Na+ concentration [Na+](i) was also inhibited by CPZ with a similar potency. Furthermore, the binding of [3H]nicotine to PC12 cells was inhibited by CPZ with an IC50 value of 2.7 ± 0.6 μM, suggesting that the nAChRs themselves are inhibited by CPZ. In addition, both 70 mM K+-induced [3H]NE secretion and [Ca2+](i) increase were inhibited by CPZ with IC50 of 7.9 ± 1.1 and 6.2 ± 0.3 μM, 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. Copyright (C) 1999 Elsevier Science Inc.

KW - Catecholamine secretion

KW - Chlorpromazine

KW - L-type Ca channels

KW - Nicotinic receptor

KW - PC12 cells

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U2 - 10.1016/S0006-2952(99)00181-1

DO - 10.1016/S0006-2952(99)00181-1

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C2 - 10509754

AN - SCOPUS:0032798014

SN - 0006-2952

VL - 58

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JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

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