Spatial and temporal expression of tachykinins and NK1- and NK2-receptor gene during TNB induced colitis in rats.
The distribution and modification of the tachykinins Substance P (SP) and neurokinin A (NKA), their precursor beta-preprotachykinins (beta-PPT) and the receptors involved in their activity, NK-1 and NK-2, were studied in trinitrobenzensulphonic acid (TNB) colitis. Rats were intrarectally treated with a 120 mg/ml of TNB solution and sacrificed at various times after colitis induction. During the acute phases of colitis, a marked decrease in tissue SP and NKA levels were observed along with an increased transcription of beta-PPT mRNA in the neurons of the myenteric plexus and an increased myeloperoxidase activity, which is an index of the tissue's inflammatory status. De novo expression of both NK(1) and NK(2) receptor mRNA was observed during the acute phase of TNB-colitis in mesenchymal cells around dilated submucosal vessels but their expression in smooth muscle cells of the muscularis mucosae and propria was moderately down-regulated. The peptide levels, myeloperoxidase activity and gene expression of tachykinin receptors were then restored during the late phases (2-4 weeks after the apten administration) while beta-PPT mRNA remained highly expressed in the myenteric plexus ganglia showing that SP and NKA are involved in repair processes. These results point to the enhanced release of tachykinins during the initial phase of colitis and a restoration of this neuropeptide pool in the healing of the tissue.
Evangelista
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S
Department of Pharmacology, Menarini Ricerche S.p.A., Via Sette Santi 1, 50131 Florence, Italy. sevangelista@menarini-ricerche.it
Tramontana
M
M
Maggi
C A
CA
D000818:Animals; D001835:Body Weight; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000235:genetics / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase