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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 2/2011

01-02-2011 | Original Article

Lubiprostone Reverses the Inhibitory Action of Morphine on Mucosal Secretion in Human Small Intestine

Authors: 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, Ryuji Ueno, Jackie D. Wood

Published in: Digestive Diseases and Sciences | Issue 2/2011

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Abstract

Background and Aims

Treatments with morphine or opioid agonists cause constipation. Lubiprostone is approved for treatment of adult idiopathic constipation and constipation-predominant 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 (ΔIsc) 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 μM, evoked increases in Isc in concentration-dependent 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.
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Metadata
Title
Lubiprostone Reverses the Inhibitory Action of Morphine on Mucosal Secretion in Human Small Intestine
Authors
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
Ryuji Ueno
Jackie D. Wood
Publication date
01-02-2011
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 2/2011
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-010-1515-8

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