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Research ArticleArticle

Effects of Lanthanides on Muscarinic Acetylcholine Receptor Function

ESAM EL-FAKAHANY and ELLIOTT RICHELSON
Molecular Pharmacology March 1981, 19 (2) 282-290;
ESAM EL-FAKAHANY
Departments of Psychiatry and Pharmacology, Mayo Foundation, Rochester, Minnesota 55901
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ELLIOTT RICHELSON
Departments of Psychiatry and Pharmacology, Mayo Foundation, Rochester, Minnesota 55901
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Abstract

Incubation of mouse neuroblastoma cells (clone N1E-115) with the lanthanides terbium, europium, neodymium, and lanthanum resulted in a concentration-dependent reduction in the maximal cyclic GMP response to full agonists of the muscarinic acetylcholine receptor, and an increase in the response to partial agonists. At 1 mM concentration these lanthanides also caused a significant decrease in the EC50 of the agonists, which was accompanied by a significant reduction in the binding affinity of the 3H-labeled antagonist quinuclidinyl benzilate (QNB), as determined for both mouse neuroblastoma cells and rat brain homogenates. However, this concentration of the lanthanides did not cause a significant change in the agonist equilibrium dissociation constant. The rank order of potency of the lanthanides for their effects on the EC50 for agonists and on the affinity of the antagonist was Tb3+ > Eu3+ > Nd3+ > La3+. Calcium ions mimicked the effects of lanthanides on the EC50 but had opposite effects on maximal responses. In addition, high calcium concentrations decreased the effects of Tb3+ on the EC50 and on [3H]QNB binding with no change in their effect on maximal cyclic GMP responses. We conclude that these lanthanides increase the efficacy of agonists, probably by interacting with Ca2+ binding sites on a factor which couples the receptor to the calcium channels; and that the lanthanides reduce maximal cyclic GMP responses to agonists by interacting with the calcium channels.

  • Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics

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Molecular Pharmacology
Vol. 19, Issue 2
1 Mar 1981
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Research ArticleArticle

Effects of Lanthanides on Muscarinic Acetylcholine Receptor Function

ESAM EL-FAKAHANY and ELLIOTT RICHELSON
Molecular Pharmacology March 1, 1981, 19 (2) 282-290;

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Research ArticleArticle

Effects of Lanthanides on Muscarinic Acetylcholine Receptor Function

ESAM EL-FAKAHANY and ELLIOTT RICHELSON
Molecular Pharmacology March 1, 1981, 19 (2) 282-290;
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