title: Effect of dehydroleucodine on intestinal transit: structural basis of the interaction with the α(2)-adrenergic receptor.
abstract: The activity of dehydroleucodine, a sesquiterpene lactone obtained from Artemisia douglasiana, was studied in mice small intestinal transit. Its mechanism was evaluated in the presence of several adrenergic and cholinergic antagonist drugs and one opioid antagonist. Docking of dehydroleucodine into the homology model of the α2-adrenergic receptor allowed us to analyze the structural basis of their interactions. The experiments showed that dehydroleucodine delayed intestinal transit. The docking of dehydroleucodine showed a unique binding site, equivalent to the binding site of carozolol in the β-adrenergic receptor. The results suggested that dehydroleucodine produced an inhibitory effect on intestinal transit. Its action could be mediated, at least in part, through the α2-adrenergic receptor.
authors.affiliation: Laboratorio de Farmacología, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, Argentina. gwendel@unsl.edu.ar
authors.forename: Graciela Haydée
authors.initials: GH
authors.lastname: Wendel
authors.forename: Alejandra Olivia
authors.initials: AO
authors.lastname: María
authors.forename: Carlos Fernando
authors.initials: CF
authors.lastname: Aguilar
authors.forename: Lilian Eugenia
authors.initials: LE
authors.lastname: Pelzer
mesh_terms: D000818:Animals; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D010646:Phentolamine / Q000037:antagonists & inhibitors; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry* / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*; D015016:Yohimbine / Q000037:antagonists & inhibitors
chemical_list: D007783:Lactones; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D012717:Sesquiterpenes; D015016:Yohimbine; C079949:dehydroleucodine; D010646:Phentolamine