Epibatidine binds with unique site and state selectivity to muscle nicotinic acetylcholine receptors.

The Journal of Biological Chemistry
R J Prince, S M Sine

Abstract

Ligand binding sites in fetal (alpha2betagammadelta) and adult (alpha2betadeltaepsilon) muscle acetylcholine receptors are formed by alphadelta, alphagamma, or alphaepsilon subunit pairs. Each type of binding site shows unique ligand selectivity due to different contributions by the delta, gamma, or epsilon subunits. The present study compares epibatidine and carbamylcholine binding in terms of their site and state selectivities for muscle receptors expressed in human embryonic kidney 293 cells. Measurements of binding to alphagamma, alphadelta, and alphaepsilon intracellular complexes reveal opposite site selectivities between epibatidine and carbamylcholine; for epibatidine the rank order of affinities is alphaepsilon > alphagamma > alphadelta, whereas for carbamylcholine the rank order is alphadelta congruent with alphaepsilon > alphagamma. Because the relative affinities of intracellular complexes resemble those of receptors in the closed activable state, the results suggest that epibatidine binds with unique site selectivity in activating the muscle receptor. Measurements of binding at equilibrium show that both enantiomers of epibatidine bind to adult and fetal receptors with shallow but monophasic binding curves. However...Continue Reading

References

Mar 1, 1992·The Journal of Membrane Biology·C J LingleJ H Steinbach
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S M Sine

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Citations

Aug 15, 2000·Behavioural Brain Research·W SihverE D London
Mar 27, 2001·Insect Biochemistry and Molecular Biology·R J LindS Wonnacott
Aug 29, 2002·The Journal of General Physiology·Richard J PrinceSteven M Sine
Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Nicolas Le NovèreJean-Pierre Changeux
Mar 23, 2001·Acta Neurologica Scandinavica. Supplementum·W SihverA Nordberg
Mar 24, 1999·The Journal of Physiology·F N SalamoneA Auerbach
Oct 31, 2006·Toxicon : Official Journal of the International Society on Toxinology·Amani CheikhChristian Cognard
Dec 18, 2007·Biochemical and Biophysical Research Communications·Hideki KawaiMichael A Raftery
Sep 24, 1998·Biophysical Journal·R J Prince, S M Sine
Oct 22, 2004·Molecular Pharmacology·Richard A PenningtonRichard J Prince
Aug 28, 2002·The Journal of Biological Chemistry·Irmgard Ursula WillcocksonSteen E Pedersen

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