Changes in preprotachykinin mRNA expression and substance P levels in dorsal root ganglia of monoarthritic rats: comparison with changes in synovial substance P levels.
We have measured changes in the expression of gamma-preprotachykinin mRNA and levels of the neuropeptide substance P in the lumbar 4 and 5 dorsal root ganglia at various time points following the induction of an antigenic monoarthritis in the rat knee. The results were compared with changes in substances P levels in the knee joint synovium during acute and chronic phases of the disease. On day 3 post-induction, there was a significant increase in the expression of gamma-preprotachykinin mRNA in the dorsal root ganglia. Concomitant with this increase in message was a rise in the levels of substance P in the dorsal root ganglia. On days 7, 10 and 21, mRNA expression had returned to control values whereas ganglion peptide levels were significantly below controls. In contrast there was little change in the total substance P levels in the synovium on days 1 and 3 despite the observed changes in the ganglia. By day 10, however, synovial levels had risen significantly above control values and remained elevated thereafter. Our results show a transitory increase in substance P synthesis after induction of an antigenic monoarthritis. This response is not mirrored in the periphery where there is no initial change in total substance P levels perhaps reflecting increased degradation be enzymes known to be present within inflamed tissue. Paradoxically synovial substance P levels are increased in the latter phases of the model which may serve to modify the inflammatory response.
Garrett
N E
NE
Department of Pharmacology, Queen Mary and Westfield College, London, UK.
Kidd
B L
BL
Cruwys
S C
SC
Tomlinson
D R
DR
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D015152:Blotting, Northern; D005727:Ganglia, Spinal / Q000378:metabolism*; D008297:Male; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D015320:Tachykinins / Q000096:biosynthesis*
D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P