Lubiprostone is a bicyclic fatty acid derivative of prostaglandin E1 used for the treatment of chronic idiopathic constipation and constipation predominant irritable bowel syndrome.1,2 The underlying mechanism of lubiprostone is stimulation of electrogenic chloride secretion by activating chloride channel type-2 (ClC-2)3 and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels4 in the apical membrane of the intestinal epithelial cells. Activation of ClC-2 channels or CFTR chloride channels in intestinal epithelial cells produces an active secretion of chloride ions from cells into the intestinal lumen followed by a passive secretion of electrolytes and water which increases the liquidity of the luminal contents. The luminal distension by increased intestinal fluid promotes the gastrointestinal (GI) tract motility which in turn increases the intestinal and colonic transit. Lubiprostone also has an effect on cystic fibrosis tissue by independent CFTR chloride channels.5 Lubiprostone induced chloride secretory action is mediated by direct activation of ClC-2 channels as well as stimulation of these channels through activating prostaglandin receptors. Besides, lubiprostone enhances and stimulates contraction in colonic as well as gastric muscles through prostaglandin E receptors (EP1 or EP4),6 suggesting the modulatory effects of lubiprostone on GI motility through the activation of prostaglandin receptors.
In this issue of Journal of Neurogastroenterology and Motility, Chan and Mashimo7 investigated the effects of lubiprostone on intestinal smooth muscle contractions and pyloric sphincter tones from murine. They found that lubiprostone increased electrical field stimulation-induced contractions of intestinal circular smooth muscles and pyloric sphincter basal tone but not intestinal longitudinal smooth muscles. The excitatory effects of lubiprostone on intestinal circular smooth muscle and pyloric sphincter basal tone were blocked by EP1 antagonist. They speculated that lubiprostone can change the GI motility by prostaglandin receptor activation and the excitatory action of lubiprostone may be another mechanism for the increased intestinal transit and the delayed gastric emptying by lubiprostone.8 Although this study provides that lubiprostone has a role as a prokinetic agent in GI tract, the underlying mechanisms of modulating contractions were not evaluated. Many cells of GI tract express E-type prostanoid receptors including smooth muscle, neuron, macrophage and interstitial cells of Cajal that contribute to modulation of GI motility.9-11 Therefore, to evaluate the clinical effects of lubiprostone for modulating GI motility, further basic studies should be carried out to find underlying mechanisms.
Footnotes
Financial support: None.
Conflicts of interest: None.
References
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