title: Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors.
abstract: Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP(3) prostanoid receptor is specifically activated by ricinoleic acid and that it mediates the pharmacological effects of castor oil. In mice lacking EP(3) receptors, the laxative effect and the uterus contraction induced via ricinoleic acid are absent. Although a conditional deletion of the EP(3) receptor gene in intestinal epithelial cells did not affect castor oil-induced diarrhea, mice lacking EP(3) receptors only in smooth-muscle cells were unresponsive to this drug. Thus, the castor oil metabolite ricinoleic acid activates intestinal and uterine smooth-muscle cells via EP(3) prostanoid receptors. These findings identify the cellular and molecular mechanism underlying the pharmacological effects of castor oil and indicate a role of the EP(3) receptor as a target to induce laxative effects.
authors.affiliation: Department of Pharmacology,  Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim,  Germany.
authors.forename: Sorin
authors.initials: S
authors.lastname: Tunaru
authors.forename: Till F
authors.initials: TF
authors.lastname: Althoff
authors.forename: Rolf M
authors.initials: RM
authors.lastname: Nüsing
authors.forename: Martin
authors.initials: M
authors.lastname: Diener
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
mesh_terms: D000818:Animals; D016466:CHO Cells; D002368:Castor Oil / Q000737:chemistry* / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D009213:Myography; D010528:Peristalsis / Q000187:drug effects*; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012277:Ricinoleic Acids / Q000032:analysis / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D058308:Receptors, Prostaglandin E, EP3 Subtype; D012277:Ricinoleic Acids; D002368:Castor Oil; C030521:ricinoleic acid