PT  - JOURNAL ARTICLE
AU  - Spalding, Tracy A.
AU  - Trotter, Carol
AU  - Skjærbæk, Niels
AU  - Messier, Terri L.
AU  - Currier, Erika A.
AU  - Burstein, Ethan S.
AU  - Li, Donghui
AU  - Hacksell, Uli
AU  - Brann, Mark R.
TI  - Discovery of an Ectopic Activation Site on the M<sub>1</sub>Muscarinic Receptor
AID  - 10.1124/mol.61.6.1297
DP  - 2002 Jun 01
TA  - Molecular Pharmacology
PG  - 1297--1302
VI  - 61
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/61/6/1297.short
4100  - http://molpharm.aspetjournals.org/content/61/6/1297.full
SO  - Mol Pharmacol2002 Jun 01; 61
AB  - Receptors have well-conserved regions that are recognized and activated by hormones and neurotransmitters. Most drugs bind to these sites and mimic or block the action of the native ligands. Using a high-throughput functional screen, we identified a potent and selective M1 muscarinic receptor agonist from a novel structural class. Using a series of chimeric receptors, we demonstrated that this ligand activates the receptor through a region that is not conserved among receptor subtypes, explaining its unprecedented selectivity. This region of the receptor is distinct from the conserved region that is recognized by traditional ligands. The finding that receptors for small-molecule transmitters can have multiple, structurally distinct activation sites has broad implications for the study of receptor structure/function and the potential for the discovery of novel ligands with high selectivity.