ArticleDigestive diseases and sciences2011
Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in human small intestine.
Article in Digestive diseases and sciences, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- A randomized, placebo-controlled trial of lubiprostone for opioid-induced constipation in chronic noncancer pain.The American journal of gastroenterology · 2015Trial
- Lubiprostone vs Senna in postoperative orthopedic surgery patients with opioid-induced constipation: a double-blind, active-comparator trial.World journal of gastroenterology · 2014Trial
- A quantitative systems pharmacology model of colonic motility with applications in drug development.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- GRG Profiles: Jackie D. Wood.Digestive diseases and sciences · 2016Article
- Enteric Nervous System: Neuropathic Gastrointestinal Motility.Digestive diseases and sciences · 2016Article
- β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Lubiprostone in constipation: clinical evidence and place in therapy.Therapeutic advances in chronic disease · 2015Review
- Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Clinical potential of naloxegol in the management of opioid-induced bowel dysfunction.Clinical and experimental gastroenterology · 2014Review
- Physiology, signaling, and pharmacology of opioid receptors and their ligands in the gastrointestinal tract: current concepts and future perspectives.Journal of gastroenterology · 2014Review
- Lubiprostone Increases Small Intestinal Smooth Muscle Contractions Through a Prostaglandin E Receptor 1 (EP1)-mediated Pathway.Journal of neurogastroenterology and motility · 2013Article
- Mast cell expression of the serotonin1A receptor in guinea pig and human intestine.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
- A critical appraisal of lubiprostone in the treatment of chronic constipation in the elderly.Clinical interventions in aging · 2013Review
- Translational neuropharmacology: the use of human isolated gastrointestinal tissues.British journal of pharmacology · 2013Review
- May the truth be with you: lubiprostone as EP receptor agonist/ClC-2 internalizing "inhibitor".Digestive diseases and sciences · 2012Article
- Lubiprostone targets prostanoid signaling and promotes ion transporter trafficking, mucus exocytosis, and contractility.Digestive diseases and sciences · 2012Article
- Lubiprostone for the treatment of adults with constipation and irritable bowel syndrome.Digestive diseases and sciences · 2011Review
- Lubiprostone reverses the inhibitory action of morphine on mucosal secretion in human small intestine.Digestive diseases and sciences · 2011Article
- ClC-2 regulation of intestinal barrier function: Translation of basic science to therapeutic target.Tissue barriersReview
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsTreatments 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.
methodsFresh 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.
resultsMorphine 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 EP(4) receptors, but not at E(1), EP(1-3) receptors, partially suppressed stimulation of Isc by lubiprostone.
conclusionsAntisecretory 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.