ArticleThe Journal of clinical investigation2010
cAMP-activated Ca2+ signaling is required for CFTR-mediated serous cell fluid secretion in porcine and human airways.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- The role of CFTR in spermatogenesis and sperm quality.Nature reviews. Urology · 2026Review
- Therapeutic potential of synergistic mucociliary clearance for cystic fibrosis airways by β-adrenergic plus cholinergic agonists.The Journal of clinical investigation · 2026Article
- Respiratory Ciliary Beat Frequency in COPD: Balancing Oxidative Stress and Pharmacological Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Loss of CFTR function is associated with reduced bitter taste receptor-stimulated nitric oxide innate immune responses in nasal epithelial cells and macrophages.Frontiers in immunology · 2023Article
- Drug Repurposing for Cystic Fibrosis: Identification of Drugs That Induce CFTR-Independent Fluid Secretion in Nasal Organoids.International journal of molecular sciences · 2022Article
- Cellular and molecular architecture of submucosal glands in wild-type and cystic fibrosis pigs.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model.Scientific reports · 2021Article
- CLCA1 Regulates Airway Mucus Production and Ion Secretion Through TMEM16A.International journal of molecular sciences · 2021Article
- PAR-2-activated secretion by airway gland serous cells: role for CFTR and inhibition byAmerican journal of physiology. Lung cellular and molecular physiology · 2021Article
- Advances in CaExperimental and therapeutic medicine · 2020Review
- Article
- Targeting the phosphoinositide-3-kinase/protein kinase B pathway in airway innate immunity.World journal of biological chemistry · 2020Review
- Acidic Submucosal Gland pH and Elevated Protein Concentration Produce Abnormal Cystic Fibrosis Mucus.Developmental cell · 2020Article
- Neuropeptide regulation of secretion and inflammation in human airway gland serous cells.The European respiratory journal · 2020Article
- Anoctamin 1/TMEM16A controls intestinal ClExperimental & molecular medicine · 2019Article
- Activation of airway epithelial bitter taste receptors byThe Journal of biological chemistry · 2018Article
- Protease-activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Epithelial Chloride Transport by CFTR Requires TMEM16A.Scientific reports · 2017Article
- CK2 is a key regulator of SLC4A2-mediated ClPflugers Archiv : European journal of physiology · 2017Article
- Gel-forming mucins form distinct morphologic structures in airways.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cystic fibrosis (CF), which is caused by mutations in CFTR, affects many tissues, including the lung. Submucosal gland serous acinar cells are primary sites of fluid secretion and CFTR expression in the lung. Absence of CFTR in these cells may contribute to CF lung pathogenesis by disrupting fluid secretion. Here, we have isolated primary serous acinar cells from wild-type and CFTR-/- pigs and humans without CF to investigate the cellular mechanisms and regulation of fluid secretion by optical imaging. Porcine and human serous cells secrete fluid in response to vasoactive intestinal polypeptide (VIP) and other agents that raise intracellular cAMP levels; here, we have demonstrated that this requires CFTR and a cAMP-dependent rise in intracellular Ca2+ concentration ([Ca2+]i). Importantly, cAMP induced the release of Ca2+ from InsP3-sensitive Ca2+ stores also responsive to cAMP-independent agonists such as cholinergic, histaminergic, and purinergic agonists that stimulate CFTR-independent fluid secretion. This provides two types of synergism that strongly potentiated cAMP-mediated fluid secretion but differed in their CFTR dependencies. First, CFTR-dependent secretion was strongly potentiated by low VIP and carbachol concentrations that individually were unable to stimulate secretion. Second, higher VIP concentrations more strongly potentiated the [Ca2+]i responses, enabling ineffectual levels of cholinergic stimulation to strongly activate CFTR-independent fluid secretion. These results identify important molecular mechanisms of cAMP-dependent secretion, including a requirement for Ca2+ signaling, and suggest new therapeutic approaches to correct defective submucosal gland secretion in CF.
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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.