Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors.

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Tunaru S, Althoff TF, Nusing RM, Diener M, Offermanns S

Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors.

Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9179-84. doi: 10.1073/pnas.1201627109. Epub 2012 May 21.

PubMed ID

22615395 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drugs

Castor oil

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Castor oil	Prostaglandin E2 receptor EP3 subtype	Protein	Humans	Yes	Agonist Activator	Details
Castor oil	Prostaglandin E2 receptor EP4 subtype	Protein	Humans	Unknown	Agonist	Details