ArticleCell biochemistry and biophysics2013
Methadone but not morphine inhibits lubiprostone-stimulated Cl- currents in T84 intestinal cells and recombinant human ClC-2, but not CFTR Cl- currents.
Article in Cell biochemistry and biophysics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- A randomized, placebo-controlled trial of lubiprostone for opioid-induced constipation in chronic noncancer pain.The American journal of gastroenterology · 2015Trial
- Against Repurposing Methadone for Glioblastoma Therapy.Biomolecules · 2020Review
- Physiological Significance of Ion Transporters and Channels in the Stomach and Pathophysiological Relevance in Gastric Cancer.Evidence-based complementary and alternative medicine : eCAM · 2020Review
- The Use of Peripheral μ-Opioid Receptor Antagonists (PAMORA) in the Management of Opioid-Induced Constipation: An Update on Their Efficacy and Safety.Drug design, development and therapy · 2020Review
- Opioid-induced constipation: a narrative review of therapeutic options in clinical management.The Korean journal of pain · 2019Article
- Clinical Overview and Considerations for the Management of Opioid-induced Constipation in Patients With Chronic Noncancer Pain.The Clinical journal of pain · 2019Review
- New developments in the treatment of opioid-induced gastrointestinal symptoms.United European gastroenterology journal · 2018Review
- Article
- Oral methylnaltrexone is efficacious and well tolerated for the treatment of opioid-induced constipation in patients with chronic noncancer pain receiving concomitant methadone.Journal of pain research · 2018Article
- Opioids in Gastroenterology: Treating Adverse Effects and Creating Therapeutic Benefits.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2017Review
- Opioid-Related Constipation in Patients With Non-cancer Pain Syndromes: a Review of Evidence-Based Therapies and Justification for a Change in Nomenclature.Current gastroenterology reports · 2017Review
- Opioids and GI Motility-Friend or Foe?Current treatment options in gastroenterology · 2016Review
- The role of naloxegol in the management of opioid-induced bowel dysfunction.Therapeutic advances in gastroenterology · 2016Review
- Opioid-induced constipation: advances and clinical guidance.Therapeutic advances in chronic disease · 2016Review
- New Options in Constipation Management.Current oncology reports · 2015Review
- Evolving paradigms in the treatment of opioid-induced bowel dysfunction.Therapeutic advances in gastroenterology · 2015Review
- Chronic opioid induced constipation in patients with nonmalignant pain: challenges and opportunities.Therapeutic advances in gastroenterology · 2015Review
- Lubiprostone in constipation: clinical evidence and place in therapy.Therapeutic advances in chronic disease · 2015Review
- A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa.Pharmacology research & perspectives · 2015Article
- Genetic Ablation of the ClC-2 Cl- Channel Disrupts Mouse Gastric Parietal Cell Acid Secretion.PloS one · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In clinical trials, methadone, but not morphine, appeared to prevent beneficial effects of lubiprostone, a ClC-2 Cl(-) channel activator, on opioid-induced constipation. Effects of methadone and morphine on lubiprostone-stimulated Cl(-) currents were measured by short circuit current (Isc) across T84 cells. Whole cell patch clamp of human ClC-2 (hClC-2) stably expressed in HEK293 cells and in a high expression cell line (HEK293EBNA) as well as human CFTR (hCFTR) stably expressed in HEK293 cells was used to study methadone and morphine effects on recombinant hClC-2 and hCFTR Cl(-) currents. Methadone but not morphine inhibited lubiprostone-stimulated Isc in T84 cells with half-maximal inhibition at 100 nM. Naloxone did not affect lubiprostone stimulation or methadone inhibition of Isc. Lubiprostone-stimulated Cl(-) currents in hClC-2/HEK293 cells, but not forskolin/IBMX-stimulated Cl(-) currents in hCFTR/HEK293 cells, were inhibited by methadone, but not morphine. HEK293EBNA cells expressing hClC-2 showed time-dependent, voltage-activated, CdCl2-inhibited Cl(-) currents in the absence (control) and the presence of lubiprostone. Methadone, but not morphine, inhibited control and lubiprostone-stimulated hClC-2 Cl(-) currents with half-maximal inhibition at 100 and 200-230 nM, respectively. Forskolin/IBMX-stimulated hClC-2 Cl(-) currents were also inhibited by methadone. Myristoylated protein kinase inhibitor (a specific PKA inhibitor) inhibited forskolin/IBMX- but not lubiprostone-stimulated hClC-2 Cl(-) currents. Methadone caused greater inhibition of lubiprostone-stimulated currents added before patching (66.1 %) compared with after patching (28.7 %). Methadone caused inhibition of lubiprostone-stimulated Cl(-) currents in T84 cells and control; lubiprostone- and forskolin/IBMX-stimulated recombinant hClC-2 Cl(-) currents may be the basis for reduced efficacy of lubiprostone in methadone-treated patients.
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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.