Hyperosmolar solutions stimulate mucus secretion in the ferret trachea.
OBJECTIVE
Inhalation of hypertonic saline or mannitol solutions acutely increases mucociliary clearance. Because increased clearance is often coupled with increased mucus secretion, we hypothesized that hyperosmolar agents would stimulate mucus secretion.


METHODS
The isolated tracheae of healthy young adult ferrets were studied in a basic research laboratory.


RESULTS
We demonstrated that there was a dose-dependent increase in mucin secretion by enzyme-linked lectin assay after incubation with 1.69 g/dL (597 mOsm/L), 3.69 g/dL (1,192 mOsm/L), 5.69 g/dL (1,823 mOsm/L), and 10.69 g/dL (3,612 mOsm/L) of saline solution over Krebs-Henseleit solution control (288 mOsm/L) [p < 0.01 for 1.69 g/dL of saline solution and p < 0.0001 for others]. Mannitol solution, 15 g/dL (1,040 mOsm/L), also significantly increased mucin secretion (n = 4, p < 0.005). There was a 47% and 54% increase in secretion of the serous cell product lysozyme after exposure to 3.69 g/dL (1,192 mOsm/L) and 10.69 g/dL (3,612 mOsm/L) saline solutions, respectively (n = 5, p < 0.05). Secretion was only stimulated when the hyperosmolar exposure was on the luminal side of the epithelium. Mucin secretion was induced within minutes of 3.69 g/dL of saline solution exposure, and this increased mucin secretion quickly peaked. The ratio of mucin to lysozyme secretion was approximately 2. This ratio appeared to be independent of the osmotic concentration of the stimulus and therefore of secretory rate.


CONCLUSIONS
Mucus secretion is markedly stimulated in response to hyperosmolarity. This may be a protective response. These results also suggest that the therapeutic use of hyperosmolar aerosols should be evaluated with care when used for patients with mucus hypersecretion and impaired mucus clearance.
Kishioka
Chikako
C
Department of Otolaryngology, Mie University School of Medicine, Tsu, Mie, Japan.
Okamoto
Kosuke
K
Kim
Jung-Soo
JS
Rubin
Bruce K
BK
D000818:Animals; D005260:Female; D005289:Ferrets; D005947:Glucose / Q000494:pharmacology; D006982:Hypertonic Solutions; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D009113:Muramidase / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D013268:Stimulation, Chemical; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*; D014325:Tromethamine / Q000494:pharmacology
D006982:Hypertonic Solutions; C074097:Krebs-Henseleit solution; D009077:Mucins; D012462:Saline Solution, Hypertonic; D014325:Tromethamine; D008353:Mannitol; D009113:Muramidase; D005947:Glucose