ArticleThe Journal of pharmacology and experimental therapeutics2010
Lubiprostone reverses the inhibitory action of morphine on intestinal secretion in guinea pig and mouse.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain.Pain medicine (Malden, Mass.) · 2014Trial
- Opioid-Induced Constipation: Mechanistic Insights, Experimental Models, and Future Perspectives.Biomedicines · 2026Review
- Progresses in Questing for the Truth of Opioid-Related Constipation in Cancer Patients.Journal of cellular and molecular medicine · 2025Review
- Therapeutic Strategies for MASH: An Update on Drug Candidates Under Investigation in Late-Phase Clinical Trials.International journal of translational medicine (Basel, Switzerland) · 2025Article
- The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target.International journal of molecular sciences · 2021Review
- Endotoxins and Non-Alcoholic Fatty Liver Disease.Frontiers in endocrinology · 2021Review
- Mu and Delta Opioid Receptors Are Coexpressed and Functionally Interact in the Enteric Nervous System of the Mouse Colon.Cellular and molecular gastroenterology and hepatology · 2020Article
- Article
- Phenylquinoxalinone CFTR activator as potential prosecretory therapy for constipation.Translational research : the journal of laboratory and clinical medicine · 2017Article
- Luminally Acting Agents for Constipation Treatment: A Review Based on Literatures and Patents.Frontiers in pharmacology · 2017Review
- Insights into the Role of Opioid Receptors in the GI Tract: Experimental Evidence and Therapeutic Relevance.Handbook of experimental pharmacology · 2017Review
- Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.Journal of neurogastroenterology and motility · 2016Article
- GRG Profiles: Jackie D. Wood.Digestive diseases and sciences · 2016Article
- CFTR activator increases intestinal fluid secretion and normalizes stool output in a mouse model of constipation.Cellular and molecular gastroenterology and hepatology · 2016Article
- Role of Quercetin in Modulating Chloride Transport in the Intestine.Frontiers in physiology · 2016Article
- Neurochemical features of endomorphin-2-containing neurons in the submucosal plexus of the rat colon.World journal of gastroenterology · 2015Article
- Lubiprostone in constipation: clinical evidence and place in therapy.Therapeutic advances in chronic disease · 2015Review
- Molecular physiology of enteric opioid receptors.American journal of gastroenterology supplements (Print) · 2014Review
- Dietary glutamate: interactions with the enteric nervous system.Journal of neurogastroenterology and motility · 2014Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Lubiprostone activates ClC-2 chloride channels in epithelia. It is approved for treatment of chronic idiopathic constipation in adults and constipation-predominate irritable bowel syndrome in women. We tested a hypothesis that lubiprostone can reverse the constipating action of morphine and investigated the mechanism of action. Short-circuit current (Isc) was recorded in Ussing chambers as a marker for chloride secretion during pharmacological interactions between morphine and lubiprostone. Measurements of fecal wet weight were used to obtain information on morphine-lubiprostone interactions in conscious mice. Morphine decreased basal Isc, with an IC(50) of 96.1 nM. The action of dimethylphenylpiperazinium (DMPP), a nicotinic receptor agonist that stimulates neurogenic Isc, was suppressed by morphine. Lubiprostone applied after pretreatment with morphine reversed morphine suppression of both basal Isc and DMPP-evoked chloride secretion. Electrical field stimulation (EFS) of submucosal neurons evoked biphasic increases in Isc. Morphine abolished the first phase and marginally suppressed the second phase. Lubiprostone reversed, in concentration-dependent manner, the action of morphine on the first and second phases of the EFS-evoked responses. Subcutaneous lubiprostone increased fecal wet weight and numbers of pellets expelled. Morphine significantly reduced fecal wet weight and number of pellets. Injection of lubiprostone, 30-min after morphine, reversed morphine-induced suppression of fecal wet weight. We conclude that inhibitory action of morphine on chloride secretion reflects suppression of excitability of cholinergic secretomotor neurons in the enteric nervous system. Lubiprostone, which does not directly affect enteric neurons, bypasses the neurogenic constipating effects of morphine by directly opening chloride channels in the mucosal epithelium.
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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.