title: Functional modulation of glycine receptors by the alkaloid gelsemine.
abstract: Gelsemine is one of the principal alkaloids produced by the Gelsemium genus of plants belonging to the Loganiaceae family. The extracts of these plants have been used for many years, for a variety of medicinal purposes. Coincidentally, recent studies have shown that gelsemine exerts anxiolytic and analgesic effects on behavioural models. Several lines of evidence have suggested that these beneficial actions were dependent on glycine receptors, which are inhibitory neurotransmitter-gated ion channels of the CNS. However, it is currently unknown whether gelsemine can directly modulate the function of glycine receptors.
  
  
  
  We examined the functional effects of gelsemine on glycine receptors expressed in transfected HEK293 cells and in cultured spinal neurons by electrophysiological techniques.
  
  
  
  Gelsemine directly modulated recombinant and native glycine receptors and exerted conformation-specific and subunit-selective effects. Gelsemine modulation was voltage-independent and was associated with differential changes in the apparent affinity for glycine and in the open probability of the ion channel. In addition, the alkaloid preferentially targeted glycine receptors in spinal neurons and showed only minor effects on GABAA and AMPA receptors. Furthermore, gelsemine significantly diminished the frequency of glycinergic and glutamatergic synaptic events without altering the amplitude.
  
  
  
  Our results provide a pharmacological basis to explain, at least in part, the glycine receptor-dependent, beneficial and toxic effects of gelsemine in animals and humans. In addition, the pharmacological profile of gelsemine may open new approaches to the development of subunit-selective modulators of glycine receptors.
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Cesar O
authors.initials: CO
authors.lastname: Lara
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Murath
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Braulio
authors.initials: B
authors.lastname: Muñoz
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Marileo
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Loreto San
authors.initials: LS
authors.lastname: Martín
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Victoria P
authors.initials: VP
authors.lastname: San Martín
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Burgos
authors.affiliation: Department of Pharmacology, School of Medicine, University of Talca, Chile.
authors.forename: Trinidad A
authors.initials: TA
authors.lastname: Mariqueo
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Aguayo
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Fuentealba
authors.affiliation: IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.
authors.forename: Patricio
authors.initials: P
authors.lastname: Godoy
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Guzman
authors.affiliation: Department of Physiology, Faculty of Biological Sciences, University of Concepcion, Chile.
authors.forename: Gonzalo E
authors.initials: GE
authors.lastname: Yévenes
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D018009:Receptors, Glycine / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D018009:Receptors, Glycine; C063230:gelsemine