Effect of dexamethasone treatment on the regional distribution of neutral endopeptidase activity in the rat trachea.
Treating rats with the glucocorticoid dexamethasone has been shown to reduce the amount of plasma extravasation produced in the trachea by tachykinins released from sensory nerves. We sought to determine whether dexamethasone works by increasing the activity of neutral endopeptidase (NEP), the principal enzyme thought to be responsible for degrading tachykinins in the airways. Rats were treated for 2 days with either saline or 4 mg/kg/day of dexamethasone, a dose we found to be maximally effective in reducing tachykinin-induced plasma extravasation. The tracheas were then removed and processed to reveal NEP-specific histofluorescence. Tissue sections were photographed through a fluorescence microscope, and the relative intensity of fluorescent staining was quantified in five regions of the tracheal wall using computerized image analysis. In the saline-treated rats, the rank order of fluorescent staining was perichondrium > chondrocytes = submucosal >> epithelium > lamina propria. Neither the amount nor distribution of NEP fluorescence was altered in the dexamethasone-treated rats. Biochemical measurements of NEP activity in tracheal homogenates (nmol product/h/mg protein) likewise revealed no significant difference between the two groups (34.1 +/- 3.5 vs 29.0 +/- 3.2; mean +/- SEM, n = 8). These findings suggest that dexamethasone may be working through a mechanism unrelated to NEP activation.
Brokaw
J J
JJ
Department of Anatomy, Indiana University School of Medicine, Evansville 47712, USA.
Werner
L M
LM
Miller
R
R
White
G W
GW
D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000201:enzymology; D005260:Female; D006651:Histocytochemistry; D008856:Microscopy, Fluorescence; D015260:Neprilysin / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution; D014132:Trachea / Q000187:drug effects / Q000201:enzymology*
D003907:Dexamethasone; D015260:Neprilysin