PMID: 9547368May 9, 1998Paper

The relationship between agonist intrinsic activity and the rate of endocytosis of muscarinic receptors in a human neuroblastoma cell line

Molecular Pharmacology
P G SzekeresJ M Edwardson

Abstract

The molecular mechanisms underlying the internalization of G protein-coupled receptors are still poorly understood. Normally agonists but not antagonists cause internalization (defined here as a reduction in the number of receptors at the cell surface), suggesting a functional relationship between agonist activity and internalization. In this study we investigated the effects of eight muscarinic ligands on the rate constants for endocytosis and recycling of m3 muscarinic acetylcholine receptors in human SH-SY5Y neuroblastoma cells. We found that there was a linear correlation between the intrinsic activity of the ligand and its ability to increase the rate constant for endocytosis, suggesting that the same active conformation of the receptor is responsible for stimulating both second messenger generation and receptor endocytosis. In contrast, the rate constant for recycling did not depend on which agonist had triggered receptor endocytosis, suggesting that recycling is a purely constitutive process. Because receptor internalization depends on the rate constants for both endocytosis and recycling, the relationship between internalization and intrinsic activity is nonlinear. In particular, mathematical modeling of receptor traffi...Continue Reading

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Dec 19, 1995·Proceedings of the National Academy of Sciences of the United States of America·W W WangR D Howells
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Citations

Nov 23, 2006·Assay and Drug Development Technologies·Edward VerdonkVivian F Liu
Sep 6, 2000·Proceedings. Biological Sciences·J Smythies
Mar 15, 2005·The Journal of Pharmacology and Experimental Therapeutics·Leen ThielemansTheo L Peeters
Apr 28, 2005·Molecular Pharmacology·Qisheng LiuAgnes Schonbrunn
Dec 24, 2010·The Journal of Biological Chemistry·Adrian J ButcherAndrew B Tobin
Jun 21, 2008·Clinical and Experimental Pharmacology & Physiology·Natasha L GrimseyMichelle Glass
Jul 3, 1999·Trends in Pharmacological Sciences·R B ClarkR Barber
Mar 9, 1999·Life Sciences·J M Edwardson, P G Szekeres
Aug 17, 1999·Biochemical Pharmacology·A Christopoulos, E E El-Fakahany
Sep 11, 2004·Biochemical and Biophysical Research Communications·Tuire Olli-LähdesmäkiJaana Kallio
Mar 25, 2009·Pharmacology & Therapeutics·Sarah Grimwood, Paul R Hartig

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