Pharmacological and physiological properties of a putative ganglionic nicotinic receptor, α3β4, expressed in transfected eucaryotic cells

Eric T. Wong; Sheldon G. Holstad; Steven J. Mennerick; Stephanie E. Hong; Charles F. Zorumski; Keith E. Isenberg

doi:10.1016/0169-328X(94)00189-L

Pharmacological and physiological properties of a putative ganglionic nicotinic receptor, α₃β₄, expressed in transfected eucaryotic cells

Eric T. Wong, Sheldon G. Holstad, Steven J. Mennerick, Stephanie E. Hong, Charles F. Zorumski, Keith E. Isenberg

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

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Abstract

Neuronal nicotinic acetylcholine receptor subunits α₃ (PCA48E) and β₄S (ZPC13) were expressed in human embryonic kidney (HEK)-293 cells by calcium phosphate transfection. In the presence of atropine, acetylcholine (ACh) induced fast activating currents which exhibited desensitization and inward rectification. The EC₅₀ for ACh was 202 ± 32 μM with a Hill coefficient of 1.9 ± 0.4. The rank order of nicotinic agonist potency was 1,1-dimethyl-4-phenylpiperozinium (DMPP) > cytisine = nicotine ≊ ACh. The maximal response elicited by DMPP was substantially less than that elicited by other agonists, suggesting that DMPP is a partial agonist. ACh (500 μM) responses were very effectively blocked by equimolar concentrations (100 μM) of the ganglionic antagonists d-tubocurarine, mecamylamine and hexamethonium. Equal concentrations of the potent muscle receptor antagonist decamethonium and the competitive antagonist dihydro-β-erythroidine were much less effective. α bungarotoxin (1 μM) had little effect on ACh-induced responses. This physiological and pharmacological profile is consistent with a ganglionic nicotinic response.

Original language	English
Pages (from-to)	101-109
Number of pages	9
Journal	Molecular Brain Research
Volume	28
Issue number	1
DOIs	https://doi.org/10.1016/0169-328X(94)00189-L
State	Published - Jan 1995

Keywords

Agonist efficacy
Agonist potency
Desensitization
Ganglionic antagonists
Muscarinic receptor
Nicotinic receptor expression
α Bungarotoxin

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10.1016/0169-328X(94)00189-L

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title = "Pharmacological and physiological properties of a putative ganglionic nicotinic receptor, α3β4, expressed in transfected eucaryotic cells",

abstract = "Neuronal nicotinic acetylcholine receptor subunits α3 (PCA48E) and β4S (ZPC13) were expressed in human embryonic kidney (HEK)-293 cells by calcium phosphate transfection. In the presence of atropine, acetylcholine (ACh) induced fast activating currents which exhibited desensitization and inward rectification. The EC50 for ACh was 202 ± 32 μM with a Hill coefficient of 1.9 ± 0.4. The rank order of nicotinic agonist potency was 1,1-dimethyl-4-phenylpiperozinium (DMPP) > cytisine = nicotine ≊ ACh. The maximal response elicited by DMPP was substantially less than that elicited by other agonists, suggesting that DMPP is a partial agonist. ACh (500 μM) responses were very effectively blocked by equimolar concentrations (100 μM) of the ganglionic antagonists d-tubocurarine, mecamylamine and hexamethonium. Equal concentrations of the potent muscle receptor antagonist decamethonium and the competitive antagonist dihydro-β-erythroidine were much less effective. α bungarotoxin (1 μM) had little effect on ACh-induced responses. This physiological and pharmacological profile is consistent with a ganglionic nicotinic response.",

keywords = "Agonist efficacy, Agonist potency, Desensitization, Ganglionic antagonists, Muscarinic receptor, Nicotinic receptor expression, α Bungarotoxin",

author = "Wong, {Eric T.} and Holstad, {Sheldon G.} and Mennerick, {Steven J.} and Hong, {Stephanie E.} and Zorumski, {Charles F.} and Isenberg, {Keith E.}",

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AU - Wong, Eric T.

AU - Holstad, Sheldon G.

AU - Mennerick, Steven J.

AU - Hong, Stephanie E.

AU - Zorumski, Charles F.

AU - Isenberg, Keith E.

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N2 - Neuronal nicotinic acetylcholine receptor subunits α3 (PCA48E) and β4S (ZPC13) were expressed in human embryonic kidney (HEK)-293 cells by calcium phosphate transfection. In the presence of atropine, acetylcholine (ACh) induced fast activating currents which exhibited desensitization and inward rectification. The EC50 for ACh was 202 ± 32 μM with a Hill coefficient of 1.9 ± 0.4. The rank order of nicotinic agonist potency was 1,1-dimethyl-4-phenylpiperozinium (DMPP) > cytisine = nicotine ≊ ACh. The maximal response elicited by DMPP was substantially less than that elicited by other agonists, suggesting that DMPP is a partial agonist. ACh (500 μM) responses were very effectively blocked by equimolar concentrations (100 μM) of the ganglionic antagonists d-tubocurarine, mecamylamine and hexamethonium. Equal concentrations of the potent muscle receptor antagonist decamethonium and the competitive antagonist dihydro-β-erythroidine were much less effective. α bungarotoxin (1 μM) had little effect on ACh-induced responses. This physiological and pharmacological profile is consistent with a ganglionic nicotinic response.

AB - Neuronal nicotinic acetylcholine receptor subunits α3 (PCA48E) and β4S (ZPC13) were expressed in human embryonic kidney (HEK)-293 cells by calcium phosphate transfection. In the presence of atropine, acetylcholine (ACh) induced fast activating currents which exhibited desensitization and inward rectification. The EC50 for ACh was 202 ± 32 μM with a Hill coefficient of 1.9 ± 0.4. The rank order of nicotinic agonist potency was 1,1-dimethyl-4-phenylpiperozinium (DMPP) > cytisine = nicotine ≊ ACh. The maximal response elicited by DMPP was substantially less than that elicited by other agonists, suggesting that DMPP is a partial agonist. ACh (500 μM) responses were very effectively blocked by equimolar concentrations (100 μM) of the ganglionic antagonists d-tubocurarine, mecamylamine and hexamethonium. Equal concentrations of the potent muscle receptor antagonist decamethonium and the competitive antagonist dihydro-β-erythroidine were much less effective. α bungarotoxin (1 μM) had little effect on ACh-induced responses. This physiological and pharmacological profile is consistent with a ganglionic nicotinic response.

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KW - Desensitization

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KW - Muscarinic receptor

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Pharmacological and physiological properties of a putative ganglionic nicotinic receptor, α₃β₄, expressed in transfected eucaryotic cells

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Keywords

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