ArticlePflugers Archiv : European journal of physiology2008
Substance P stimulates CFTR-dependent fluid secretion by mouse tracheal submucosal glands.
Article in Pflugers Archiv : European journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Pulmonary neuroendocrine cells sense succinate to stimulate myoepithelial cell contraction.Developmental cell · 2022Article
- Lipopolysaccharides induce a RAGE-mediated sensitization of sensory neurons and fluid hypersecretion in the upper airways.Scientific reports · 2021Article
- Nebulized hypertonic saline triggers nervous system-mediated active liquid secretion in cystic fibrosis swine trachea.Scientific reports · 2019Article
- Neuropeptides in asthma, chronic obstructive pulmonary disease and cystic fibrosis.Respiratory research · 2018Review
- Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens.Nature communications · 2017Article
- Taste receptors in innate immunity.Cellular and molecular life sciences : CMLS · 2015Review
- Pseudomonas aeruginosa triggers CFTR-mediated airway surface liquid secretion in swine trachea.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease.Physiological reviews · 2014Review
- Protein phosphatase 1 coordinates CFTR-dependent airway epithelial HCO3- secretion by reciprocal regulation of apical and basolateral membrane Cl(-)-HCO3- exchangers.British journal of pharmacology · 2013Article
- Cellular mechanism underlying formaldehyde-stimulated Cl- secretion in rat airway epithelium.PloS one · 2013Article
- Why mouse airway submucosal gland serous cells do not secrete fluid in response to cAMP stimulation.The Journal of biological chemistry · 2012Article
- CGRP induction in cystic fibrosis airways alters the submucosal gland progenitor cell niche in mice.The Journal of clinical investigation · 2011Article
- Functional regulation of cystic fibrosis transmembrane conductance regulator-containing macromolecular complexes: a small-molecule inhibitor approach.The Biochemical journal · 2011Article
- Control of enteric neuromuscular functions by purinergic A(3) receptors in normal rat distal colon and experimental bowel inflammation.British journal of pharmacology · 2010Article
- A new role for bicarbonate secretion in cervico-uterine mucus release.The Journal of physiology · 2010Article
- Compartmentalized cyclic adenosine 3',5'-monophosphate at the plasma membrane clusters PDE3A and cystic fibrosis transmembrane conductance regulator into microdomains.Molecular biology of the cell · 2010Article
- Effects of secretagogues on net and unidirectional liquid fluxes across porcine bronchial airways.American journal of physiology. Lung cellular and molecular physiology · 2010Article
- Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process.The Journal of clinical investigation · 2009Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
The mucosa of the proximal airways defends itself and the lower airways from inhaled irritants such as capsaicinoids, allergens, and infections by several mechanisms. Sensory nerves monitor the luminal microenvironment and release the tachykinin substance P (SP) to stimulate mucus secretion. Here, we have studied the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in SP stimulation by comparing mouse airway submucosal gland responses in wild-type (WT) and CFTR-/- mice. Capsaicinoids (chili pepper oil) increased fluid secretion by glands from WT mice five-fold, and this response was abolished by exposing the basolateral aspect of the tracheas to L-732,138 (10 micromol/l), a specific antagonist of the neurokinin-1 receptor. Secretion was also stimulated 25-fold by basolateral application of SP, and this response was strongly inhibited by the CFTR inhibitor CFTR(inh)172. In contrast, submucosal glands from CFTR knockout mice failed to secrete when stimulated by SP (1 micromol/l), although those from wild-type control littermates were responsive. SP stimulation of wild-type glands was also abolished by clotrimazole (25 micromol/l), a blocker of Ca(2+)-activated K(+) channels. These results indicate that SP mediates local responses to capsaicinoids through a mechanism involving coordinated activation of CFTR and K(+) channels. To our knowledge, this is the first study in which CFTR-dependent responses to substance P have been directly demonstrated. Since CFTR regulation is qualitatively similar in human and mouse glands, loss of this local regulation in CF may contribute to reduced innate defenses in CF airways.
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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.