ArticleAmerican journal of physiology. Cell physiology2012
Divergent CFTR orthologs respond differently to the channel inhibitors CFTRinh-172, glibenclamide, and GlyH-101.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Seminal fluid extracellular vesicles restore human sperm osmoregulation after cystic fibrosis transmembrane conductance regulator inhibition.Scientific reports · 2025Article
- Allosteric inhibition of CFTR gating by CFTRinh-172 binding in the pore.Nature communications · 2024Article
- DRA involvement in linaclotide-stimulated bicarbonate secretion during loss of CFTR function.JCI insight · 2024Article
- Key role of down-regulated in adenoma (bioRxiv : the preprint server for biology · 2024Article
- Piperine as potential therapy of post-weaning porcine diarrheas: an in vitro study using a porcine duodenal enteroid model.BMC veterinary research · 2023Article
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- Expression and Function of ABC Proteins in Fish Intestine.Frontiers in physiology · 2021Review
- Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Human Lung Microvascular Endothelial Cells Controls Oxidative Stress, Reactive Oxygen-Mediated Cell Signaling and Inflammatory Responses.Frontiers in physiology · 2020Article
- Differential thermostability and response to cystic fibrosis transmembrane conductance regulator potentiators of human and mouse F508del-CFTR.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- In Silico Characterization of Structural Distinctions between Isoforms of Human and Mouse Sphingosine Kinases for Accelerating Drug Discovery.Journal of chemical information and modeling · 2019Article
- Structural mechanisms of CFTR function and dysfunction.The Journal of general physiology · 2018Review
- AMP-activated protein kinase and adenosine are both metabolic modulators that regulate chloride secretion in the shark rectal gland ( Squalus acanthias).American journal of physiology. Cell physiology · 2018Article
- Functional characterization reveals that zebrafish CFTR prefers to occupy closed channel conformations.PloS one · 2018Article
- A role for the cystic fibrosis transmembrane conductance regulator in the nitric oxide-dependent release of ClJournal of neurophysiology · 2017Article
- Comparative Effects of Chloride Channel Inhibitors on LRRC8/VRAC-Mediated Chloride Conductance.Frontiers in pharmacology · 2017Article
- Molecular modelling and molecular dynamics of CFTR.Cellular and molecular life sciences : CMLS · 2017Review
- Functional and molecular identification of a TASK-1 potassium channel regulating chloride secretion through CFTR channels in the shark rectal gland: implications for cystic fibrosis.American journal of physiology. Cell physiology · 2016Article
- THE SHARK RECTAL GLAND MODEL: A CHAMPION OF RECEPTOR MEDIATED CHLORIDE SECRETION THROUGH CFTR.Transactions of the American Clinical and Climatological Association · 2016Article
- Value of Organoids from Comparative Epithelia Models.The Yale journal of biology and medicine · 2015Review
- Murine and human CFTR exhibit different sensitivities to CFTR potentiators.American journal of physiology. Lung cellular and molecular physiology · 2015Article
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4 authors at 2 institutions in 1 country.
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Abstract
Comparison of diverse orthologs is a powerful tool to study the structure and function of channel proteins. We investigated the response of human, killifish, pig, and shark cystic fibrosis transmembrane conductance regulator (CFTR) to specific inhibitors of the channel: CFTR(inh)-172, glibenclamide, and GlyH-101. In three systems, including organ perfusion of the shark rectal gland, primary cultures of shark rectal gland tubules, and expression studies of each ortholog in cRNA microinjected Xenopus laevis oocytes, we observed fundamental differences in the sensitivity to inhibition by these channel blockers. In organ perfusion studies, shark CFTR was insensitive to inhibition by CFTR(inh)-172. This insensitivity was also seen in short-circuit current experiments with cultured rectal gland tubular epithelial cells (maximum inhibition 4 ± 1.3%). In oocyte expression studies, shark CFTR was again insensitive to CFTR(inh)-172 (maximum inhibition 10.3 ± 2.5% at 25 μM), pig CFTR was insensitive to glibenclamide (maximum inhibition 18.4 ± 4.4% at 250 μM), and all orthologs were sensitive to GlyH-101. The amino acid residues considered responsible by previous site-directed mutagenesis for binding of the three inhibitors are conserved in the four CFTR isoforms studied. These experiments demonstrate a profound difference in the sensitivity of different orthologs of CFTR proteins to inhibition by CFTR blockers that cannot be explained by mutagenesis of single amino acids. We believe that the potency of the inhibitors CFTR(inh)-172, glibenclamide, and GlyH-101 on the CFTR chloride channel protein is likely dictated by the local environment and the three-dimensional structure of additional residues that form the vestibules, the chloride pore, and regulatory regions of the channel.
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