SUBSTANCE-P CONTENT AND PREPROTACHYKININ GENE-1 MESSENGER-RNA EXPRESSION IN A RAT MODEL OF CHRONIC-BRONCHITIS

Chronic exposure of rats to high concentrations of SO2 gas induces a s yndrome similar to human chronic bronchitis, The aim of these studies was to determine if substance P (SP) content in the trachea or lungs w as elevated in this animal model of chronic bronchitis, and whether an increase in SP content was associated with an increase in preprotachy kinin 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 liqui d nitrogen for measurement of SP content by enzyme-linked immunosorben t assay, The SP content of the tracheas from SO2-exposed rats was 3-fo ld greater than controls (8.9 +/- 1.2 and 3.0 +/- 0.7 pmol/g tissue, r espectively; 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, resp ectively; P = 0.06), In order to determine whether SP synthesis in the cell bodies of the C-fibers innervating the trachea and lungs accompa nied a change in SP levels, thoracic dorsal root ganglia and nodose ga nglia were removed and PPT mRNA quantitated by Northern analysis. Ther e was no difference in PPT mRNA between control and SO2-exposed rats i n nodose or dorsal root ganglia. These results suggest a post transcri ptional mechanism of PPT regulation. Elevated SP levels could play a p rotective role in the responses of the airways to chronic exposure of inhaled irritants.