Central effects of selective NK1 and NK3 tachykinin receptor agonists on two models of experimentally-induced colitis in rats.
Peripheral tachykinins (TKs) are believed to play a role in the pathogenesis of inflammatory bowel diseases (IBD). In this study we investigated changes induced by central administration of two natural TK receptor agonists, NK(1) (PG-SPI) and NK(3) (PG-KII), on trinitrobenzene sulphonic acid (TNBS)- and dextran sodium sulphate (DSS)-induced experimental colitis in rats. Colitis was induced by instilling a single intracolonic dose of TNBS 50 mgkg(-1) (0.5 ml in 50% ethanol) or by oral administration of 5% DSS for 7 days. Each group of rats was intracerebroventricularly injected daily with PG-SPI and PG-KII (0.5, 5, and 50 microgkg(-1)). On day 3, TNBS-treated animals were killed and the severity of gut inflammation was evaluated by measuring myeloperoxidase (MPO) activity, interleukin-1beta (IL-1beta) production and by scoring macroscopic and histologic colonic damage. DSS-treated animals were checked daily for the length of survival and for stool consistency and faecal blood. In the TNBS group, PG-SPI and PG-KII increased scores for the severity of colonic damage, stimulated the production of IL-1beta and increased granulocyte infiltration into the colon (MPO activity). In the DSS group, PG-SPI and PG-KII decreased the percentage of surviving animals, and increased the number of rats that developed loose stools and blood in the faeces and the MPO activity. These results indicate that centrally injected NK(1) and NK(3) tachykinin receptor agonists play a proinflammatory role in experimentally-induced colitis in rats.
Improta
Giovanna
G
Department of Human Physiology and Pharmacology, University La Sapienza, Ple A. Moro 5-00185, Rome, Italy. giovanna@uniroma1.it
Carpino
Francesco
F
Petrozza
Vincenzo
V
Guglietta
Antonio
A
Tabacco
Alessandra
A
Broccardo
Maria
M
D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000819:agonists* / Q000378:metabolism; D015996:Survival Rate; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
D007375:Interleukin-1; D018039:Receptors, Tachykinin; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D009195:Peroxidase