dc.creatorIturriaga-Vásquez, Patricio
dc.creatorCarbone, Annalisa
dc.creatorGarcía Beltrán, Olimpo
dc.creatorLivingstone, Phil D.
dc.creatorBiggin, Philip C.
dc.creatorCassels Niven, Bruce
dc.creatorWonnacott, Susan
dc.creatorZapata Torres, Gerald
dc.creatorBermudez, Isabel
dc.date.accessioned2019-03-11T13:00:13Z
dc.date.available2019-03-11T13:00:13Z
dc.date.created2019-03-11T13:00:13Z
dc.date.issued2010
dc.identifierMolecular Pharmacology, Volumen 78, Issue 3, 2018, Pages 366-375
dc.identifier15210111
dc.identifier0026895X
dc.identifier10.1124/mol.110.065490
dc.identifierhttps://repositorio.uchile.cl/handle/2250/165066
dc.description.abstractThe Erythrina alkaloids erysodine and dihydro-β-erythroidine (DHβE) are potent and selective competitive inhibitors of α4β2 nicotinic acetylcholine receptors (nAChRs), but little is known about the molecular determinants of the sensitivity of this receptor subtype to inhibition by this class of antagonists. We addressed this issue by examining the effects of DHβE and a range of aromatic Erythrina alkaloids on [ 3H]cytisine binding and receptor function in conjunction with homology models of the α4β2 nAChR, mutagenesis, and functional assays. The lactone group of DHβE and a hydroxyl group at position C-16 in aromatic Erythrina alkaloids were identified as major determinants of potency, which was decreased when the conserved residue Tyr126 in loop A of the α4 subunit was substituted by alanine. Sensitivity to inhibition was also decreased by substituting the conserved aromatic residues α4Trp182 (loop B), α4Tyr230 (loop C), and β2Trp82 (loop D) and the nonconserved β2Thr84; however, only
dc.languageen
dc.publisherAmerican Society for Pharmacology and Experimental Therapy
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
dc.sourceMolecular Pharmacology
dc.subjectMolecular Medicine
dc.subjectPharmacology
dc.titleMolecular determinants for competitive inhibition of α4β2 nicotinic acetylcholine receptors
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución