On the nature of partial agonism in the nicotinic receptor superfamily Export

@article{lape:2008, abstract = {Partial agonists are ligands that bind to receptors but produce only a small maximum response even at concentrations where all receptors are occupied. In the case of ligand-activated ion channels, it has been supposed since 1957 that partial agonists evoke a small response because they are inefficient at eliciting the change of conformation between shut and open states of the channel. We have investigated partial agonists for two members of the nicotinic superfamily—the muscle nicotinic acetylcholine receptor and the glycine receptor—and find that the open–shut reaction is similar for both full and partial agonists, but the response to partial agonists is limited by an earlier conformation change ('flipping') that takes place while the channel is still shut. This has implications for the interpretation of structural studies, and in the future, for the design of partial agonists for therapeutic use.}, author = {Lape, Remigijus and Colquhoun, David and Sivilotti, Lucia G.}, citeulike-article-id = {3112744}, citeulike-linkout-0 = {http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature07139.html;jsessionid=8D1FAD38B1E64D7FC67BA9FA4FB8FD1B}, journal = {Nature}, keywords = {agonists, channel, partial}, posted-at = {2008-08-12 21:28:24}, priority = {2}, title = {On the nature of partial agonism in the nicotinic receptor superfamily}, url = {http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature07139.html;jsessionid=8D1FAD38B1E64D7FC67BA9FA4FB8FD1B}, volume = {doi:10.1038/nature07139}, year = {2008} }

TY - JOUR ID - lape:2008 L3 - citeulike-article-id:3112744 N2 - Partial agonists are ligands that bind to receptors but produce only a small maximum response even at concentrations where all receptors are occupied. In the case of ligand-activated ion channels, it has been supposed since 1957 that partial agonists evoke a small response because they are inefficient at eliciting the change of conformation between shut and open states of the channel. We have investigated partial agonists for two members of the nicotinic superfamily—the muscle nicotinic acetylcholine receptor and the glycine receptor—and find that the open–shut reaction is similar for both full and partial agonists, but the response to partial agonists is limited by an earlier conformation change (‘flipping’) that takes place while the channel is still shut. This has implications for the interpretation of structural studies, and in the future, for the design of partial agonists for therapeutic use. JF - Nature TI - On the nature of partial agonism in the nicotinic receptor superfamily VL - doi:10.1038/nature07139 KW - agonists KW - channel KW - partial AU - Lape, Remigijus AU - Colquhoun, David AU - Sivilotti, Lucia PY - 2008/// UR - http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature07139.html;jsessionid=8D1FAD38B1E64D7FC67BA9FA4FB8FD1B ER -