ArticleBritish journal of pharmacology2011
Lubiprostone targets prostanoid EP₄ receptors in ovine airways.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Lubiprostone is non-selective activator of cAMP-gated ion channels and Clc-2 has a minor role in its prosecretory effect in intestinal epithelial cells.Molecular pharmacology · 2022Article
- Receptor-mediated activation of CFTR via prostaglandin signaling pathways in the airway.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Clubbed Digits Presumably Caused by Lubiprostone.Internal medicine (Tokyo, Japan) · 2021Article
- Article
- Lubiprostone in constipation: clinical evidence and place in therapy.Therapeutic advances in chronic disease · 2015Review
- Effects of lubiprostone on pacemaker activity of interstitial cells of cajal from the mouse colon.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2014Article
- Lubiprostone Increases Small Intestinal Smooth Muscle Contractions Through a Prostaglandin E Receptor 1 (EP1)-mediated Pathway.Journal of neurogastroenterology and motility · 2013Article
- E-type prostanoid receptor 4 (EP4) in disease and therapy.Pharmacology & therapeutics · 2013Review
- Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epithelia.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Characterising the mechanism of airway smooth muscle β2 adrenoceptor desensitization by rhinovirus infected bronchial epithelial cells.PloS one · 2013Article
- May the truth be with you: lubiprostone as EP receptor agonist/ClC-2 internalizing "inhibitor".Digestive diseases and sciences · 2012Article
- Lubiprostone activates CFTR, but not ClC-2, via the prostaglandin receptor (EP(4)).Biochemical and biophysical research communications · 2012Article
- New horizons in the treatment of cystic fibrosis.British journal of pharmacology · 2011Review
- 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
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeLubiprostone, a prostaglandin E₁ derivative, is reported to activate ClC-2 chloride channels located in the apical membranes of a number of transporting epithelia. Lack of functioning CFTR chloride channels in epithelia is responsible for the genetic disease cystic fibrosis, therefore, surrogate channels that can operate independently of CFTR are of interest. This study explores the target receptor(s) for lubiprostone in airway epithelium. EXPERIMENTAL APPROACH: All experiments were performed on the ventral tracheal epithelium of sheep. Epithelia were used to measure anion secretion from the apical surface as short circuit current or as fluid secretion from individual airway submucosal glands, using an optical method. KEY
resultsThe EP₄ antagonists L-161982 and GW627368 inhibited short circuit current responses to lubiprostone, while EP₁(,)₂(&)₃ receptor antagonists were without effect. Similarly, lubiprostone induced secretion in airway submucosal glands was inhibited by L-161982. L-161982 effectively competed with lubiprostone with a K(d) value of 0.058 µM, close to its value for binding to human EP₄ receptors (0.024 µM). The selective EP₄ agonist L-902688 and lubiprostone behaved similarly with respect to EP₄ receptor antagonists. Results of experiments with H89, a protein kinase A inhibitor, were consistent with lubiprostone acting through a G(s) -protein coupled EP₄ receptor/cAMP cascade. CONCLUSIONS AND IMPLICATIONS: Lubiprostone-induced short-circuit currents and submucosal gland secretions were inhibited by selective EP₄ receptor antagonists. The results suggest EP₄ receptor activation by lubiprostone triggers cAMP production necessary for CFTR activation and the secretory responses, a possibility precluded in CF tissues.
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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.