title: Erythrina mulungu alkaloids are potent inhibitors of neuronal nicotinic receptor currents in mammalian cells.
abstract: Crude extracts and three isolated alkaloids from Erythrina mulungu plants have shown anxiolytic effects in different animal models. We investigated whether these alkaloids could affect nicotinic acetylcholine receptors and if they are selective for different central nervous system (CNS) subtypes. Screening experiments were performed using a single concentration of the alkaloid co-applied with acetylcholine in whole cell patch-clamp recordings in three different cell models: (i) PC12 cells natively expressing α3* nicotinic acetylcholine receptors; (ii) cultured hippocampal neurons natively expressing α7* nicotinic acetylcholine receptors; and (iii) HEK 293 cells heterologoulsy expressing α4β2 nicotinic acetylcholine receptors. For all three receptors, the percent inhibition of acetylcholine-activated currents by (+)-11á-hydroxyerysotrine was the lowest, whereas (+)-erythravine and (+)-11á-hydroxyerythravine inhibited the currents to a greater extent. For the latter two substances, we obtained concentration-response curves with a pre-application protocol for the α7* and α4β2 nicotinic acetylcholine receptors. The IC50 obtained with (+)-erythravine and (+)-11á-hydroxyerythravine were 6 µM and 5 µM for the α7* receptors, and 13 nM and 4 nM for the α4β2 receptors, respectively. Our data suggest that these Erythrina alkaloids may exert their behavioral effects through inhibition of CNS nicotinic acetylcholine receptors, particularly the α4β2 subtype.
authors.affiliation: Laboratório de Farmacologia Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Pedro
authors.initials: P
authors.lastname: Setti-Perdigão
authors.affiliation: Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE), Instituto de Química, Universidade Estadual Paulista Júlio de Mesquita Filho, Araraquara, Brazil.
authors.forename: Maria A R
authors.initials: MA
authors.lastname: Serrano
authors.affiliation: Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE), Instituto de Química, Universidade Estadual Paulista Júlio de Mesquita Filho, Araraquara, Brazil.
authors.forename: Otávio A
authors.initials: OA
authors.lastname: Flausino
authors.affiliation: Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE), Instituto de Química, Universidade Estadual Paulista Júlio de Mesquita Filho, Araraquara, Brazil.
authors.forename: Vanderlan S
authors.initials: VS
authors.lastname: Bolzani
authors.affiliation: Laboratório de Farmacologia Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Marília Z P
authors.initials: MZ
authors.lastname: Guimarães
authors.affiliation: Laboratório de Farmacologia Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Newton G
authors.initials: NG
authors.lastname: Castro
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004895:Erythrina / Q000737:chemistry*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic