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Authordc.contributor.authorIturriaga-Vásquez, Patricio 
Authordc.contributor.authorCarbone, Annalisa 
Authordc.contributor.authorGarcía Beltrán, Olimpo 
Authordc.contributor.authorLivingstone, Phil D. 
Authordc.contributor.authorBiggin, Philip C. 
Authordc.contributor.authorCassels Niven, Bruce 
Authordc.contributor.authorWonnacott, Susan 
Authordc.contributor.authorZapata Torres, Gerald 
Authordc.contributor.authorBermudez, Isabel 
Cita de ítemdc.identifier.citationMolecular Pharmacology, Volumen 78, Issue 3, 2018, Pages 366-375
Abstractdc.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
Publisherdc.publisherAmerican Society for Pharmacology and Experimental Therapy
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
Link to Licensedc.rights.uri
Sourcedc.sourceMolecular Pharmacology
Keywordsdc.subjectMolecular Medicine
Títulodc.titleMolecular determinants for competitive inhibition of α4β2 nicotinic acetylcholine receptors
Document typedc.typeArtículo de revista
Indexationuchile.indexArtículo de publicación SCOPUS

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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile