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Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process
Jae Young Choi, … , David Weill, Jeffrey J. Wine
Jae Young Choi, … , David Weill, Jeffrey J. Wine
Published April 20, 2009
Citation Information: J Clin Invest. 2009;119(5):1189-1200. https://doi.org/10.1172/JCI37284.
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Research Article Pulmonology

Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process

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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.

Authors

Jae Young Choi, Monal Khansaheb, Nam Soo Joo, Mauri E. Krouse, Robert C. Robbins, David Weill, Jeffrey J. Wine

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Figure 3

Secretion rates of human airway glands to SubP.

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Secretion rates of human airway glands to SubP.
(A) Approximate dose-res...
(A) Approximate dose-response relationship for submucosal gland secretion from HN glands. Each point is the average of 10–14 glands from 2–3 different HN subjects; 5 HN subjects were used for the graph, and all data were obtained within 8 hours of harvest. The secretion rate was averaged over the first 15 minutes following SubP addition. Up to 3 increasing concentrations were administered per subject. (B and C) Summary data for average secretion rates measured 15 minutes after 10 μM SubP and 5–10 minutes after 10 μM carbachol. The scale for responses to carbachol is 10 times the scale for responses to SubP. Bars in B show the secretion rate for responding glands and are labeled with the number of subjects, number of responding glands, and total number of glands tested. Five CF glands responded to SubP of more than 100 tested. The CF secretory rate for the 5 responding glands was significantly less than that for either HN or DC glands. *P < 0.05. Bars in C show the secretion rate for responding glands and are labeled with the number of subjects and total number of glands tested. Error bars are SEM (A–C).

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