Substance P content and preprotachykinin gene-I mRNA expression in a rat model of chronic bronchitis.
Chronic exposure of rats to high concentrations of SO2 gas induces a syndrome similar to human chronic bronchitis. The aim of these studies was to determine if substance P (SP) content in the trachea or lungs was elevated in this animal model of chronic bronchitis, and whether an increase in SP content was associated with an increase in preprotachykinin gene-I (PPT) mRNA expression. Rats were exposed to air (controls) or 250 ppm SO2 gas, 5 h per day, 5 days per week, for a period of 4 wk. Animals were killed and the lungs and trachea were frozen in liquid nitrogen for measurement of SP content by enzyme-linked immunosorbent assay. The SP content of the tracheas from SO2-exposed rats was 3-fold greater than controls (8.9 +/- 1.2 and 3.0 +/- 0.7 pmol/g tissue, respectively; P=0.0005), whereas the SP content of the lungs was not different (SO2 = 4.8 +/- 0.8 and air = 3.0 +/- 0.7 pmol/g tissue, respectively; P = 0.06). In order to determine whether SP synthesis in the cell bodies of the C-fibers innervating the trachea and lungs accompanied a change in SP levels, thoracic dorsal root ganglia and nodose ganglia were removed and PPT mRNA quantitated by Northern analysis. There was no difference in PPT mRNA between control and SO2-exposed rats in nodose or dorsal root ganglia. These results suggest a post-transcriptional mechanism of PPT regulation. Elevated SP levels could play a protective role in the responses of the airways to chronic exposure of inhaled irritants.
Killingsworth
C R
CR
Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Paulauskis
J D
JD
Shore
S A
SA
D000818:Animals; D001483:Base Sequence; D001991:Bronchitis / Q000139:chemically induced / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism; D015870:Gene Expression; D008168:Lung / Q000294:innervation / Q000378:metabolism; D008969:Molecular Sequence Data; D009620:Nodose Ganglion / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*; D013458:Sulfur Dioxide; D015320:Tachykinins / Q000235:genetics*; D014132:Trachea / Q000294:innervation / Q000378:metabolism
D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D013458:Sulfur Dioxide; D013373:Substance P