Lubiprostone Reverses the Inhibitory Action of Morphine on Mucosal Secretion in Human Small Intestine
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Xiaohong Sun Xiyu Wang Guo-Du Wang Yun Xia Sumei Liu Meihua Qu Bradley J. Needleman Dean J. Mikami W. Scott Melvin Laura M. Bohn
- چاپ و سال / کشور: 2010
Description
Background and Aims Treatments withmorphine or opioid agonists cause constipation. Lubiprostone is approved for treatment of adult idiopathic constipation and constipationpredominant IBS in adult women. We tested whether lubiprostone can reverse morphine-suppression of mucosal secretion in human intestine and explored the mechanism of action. Methods Fresh segments of jejunum discarded during Roux-En-Y gastric bypass surgeries were used. Changes in short-circuit current (DIsc) were recorded in Ussing flux chambers as a marker for electrogenic chloride secretion during pharmacological interactions between morphine, prostaglandin receptor antagonists, chloride channel blockers and lubiprostone. Results Morphine suppressed basal Isc. Lubiprostone reversed morphine suppression of basal Isc. Lubiprostone, applied to the mucosa in concentrations ranging from 3 nM to 30 lM, evoked increases in Isc in concentrationdependent manner when applied to the mucosal side of muscle-stripped preparations. Blockade of enteric nerves did not change stimulation of Isc by lubiprostone. Removal of chloride or application of bumetanide or NPPB suppressed or abolished responses to lubiprostone. Antagonists acting at CFTR channels and prostaglandin EP4 receptors, but not at E1, EP1-3 receptors, partially suppressed stimulation of Isc by lubiprostone. Conclusions Antisecretory action of morphine results from suppression of excitability of secretomotor neurons in the enteric nervous system. Lubiprostone, which does not affect enteric neurons directly, bypasses the action of morphine by directly opening mucosal chloride channels
Dig Dis Sci (2011) 56:330–338 DOI 10.1007/s10620-010-1515-8 Received: 9 August 2010 / Accepted: 22 November 2010 / Published online: 23 December 2010
