Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process
Open Access
- 1 May 2009
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 119 (5), 1189-1200
- https://doi.org/10.1172/jci37284
Abstract
Chronic bacterial airway infections are the major cause of mortality in cystic fibrosis (CF). Normal airway defenses include reflex stimulation of submucosal gland mucus secretion by sensory neurons that release substance P (SubP). CFTR is an anion channel involved in fluid secretion and mutated in CF; the role of CFTR in secretions stimulated by SubP is unknown. We used optical methods to measure SubP-mediated secretion from human submucosal glands in lung transplant tissue. Glands from control but not CF subjects responded to mucosal chili oil. Similarly, serosal SubP stimulated secretion in more than 60% of control glands but only 4% of CF glands. Secretion triggered by SubP was synergistic with vasoactive intestinal peptide and/or forskolin but not with carbachol; synergy was absent in CF glands. Pig glands demonstrated a nearly 10-fold greater response to SubP. In 10 of 11 control glands isolated by fine dissection, SubP caused cell volume loss, lumen expansion, and mucus flow, but in 3 of 4 CF glands, it induced lumen narrowing. Thus, in CF, the reduced ability of mucosal irritants to stimulate airway gland secretion via SubP may be another factor that predisposes the airways to infections.Keywords
This publication has 57 references indexed in Scilit:
- The porcine lung as a potential model for cystic fibrosisAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2008
- HCO3− Secretion by Murine Nasal Submucosal Gland Serous Acinar Cells during Ca2+-stimulated Fluid SecretionThe Journal of general physiology, 2008
- Production of CFTR-null and CFTR-ΔF508 heterozygous pigs by adeno-associated virus–mediated gene targeting and somatic cell nuclear transferJCI Insight, 2008
- Fluid secretion by submucosal glands of the tracheobronchial airwaysRespiratory Physiology & Neurobiology, 2007
- Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosisJCI Insight, 2007
- Optical imaging of Ca2+-evoked fluid secretion by murine nasal submucosal gland serous acinar cellsThe Journal of Physiology, 2007
- Parasympathetic control of airway submucosal glands: Central reflexes and the airway intrinsic nervous systemAutonomic Neuroscience, 2007
- Mucus secretion by single tracheal submucosal glands from normal and cystic fibrosis transmembrane conductance regulator knockout miceThe Journal of Physiology, 2007
- A small molecule CFTR inhibitor produces cystic fibrosis‐like submucosal gland fluid secretions in normal airwaysThe FASEB Journal, 2004
- Carbachol‐Stimulated Chloride Secretion in Mouse Colon: Evidence of a Role for Autocrine Prostaglandin E2 ReleaseExperimental Physiology, 2000