JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kankuri, E.
Right arrow Articles by Moilanen, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kankuri, E.
Right arrow Articles by Moilanen, E.

Vol. 298, Issue 3, 1128-1132, September 2001

Suppression of Acute Experimental Colitis by a Highly Selective Inducible Nitric-Oxide Synthase Inhibitor, N-[3-(Aminomethyl)benzyl]acetamidine

Esko Kankuri, Kirsi Vaali, Richard G. Knowles, Mari Lähde, Riitta Korpela, Heikki Vapaatalo and Eeva Moilanen

Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland (E.K., K.V., R.K., H.V.); GlaxoSmithKline Research, Medicines Research Centre, Gunnels Wood Centre, Stevenage, Hertfordshire, United Kingdom (R.G.K.); and The Immunopharmacological Research Group, Medical School, University of Tampere, and Tampere University Hospital, Tampere, Finland (M.L., E.M.)

High concentrations of nitric oxide (NO) produced by the inducible nitric-oxide synthase (iNOS) are associated with ulcerative inflammation and disease activity in colitis. Therefore, inhibition of iNOS serves as a novel experimental approach to treat gut inflammation. The aim of the present study was to investigate the effects of a novel highly selective iNOS inhibitor, N-[3-(aminomethyl)benzyl]acetamidine (1400W), as compared with a nonselective NOS inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME), in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in the rat. Increased expression of iNOS protein and mRNA was found in acute TNBS-induced colitis along with neutrophil infiltration, inflammatory edema, and tissue damage. In a 24-h model of acute colitis, subcutaneous injections of 1400W (5 or 10 mg/kg t.i.d.) produced a 56 and 95% reduction in inflammatory edema formation, a 68 and 63% reduction in neutrophil infiltration (measured as myeloperoxidase activity), and a 19 and 26% decrease in the size of mucosal lesions as compared with vehicle treatment. Administration of L-NAME (35 mg/kg) failed to produce any significant beneficial effects as compared with vehicle treatment in this experimental model of acute colitis. Treatment with 1400W, a highly selective inhibitor of iNOS, reduced formation of edema, neutrophil infiltration, and macroscopic inflammatory damage in experimentally induced acute colitis in the rat. In contrast, nonselective nitric-oxide synthase inhibition with L-NAME provided no benefit. These results support the idea that selective iNOS inhibitors have a promise in the treatment of colitis.

0022-3565/01/2983-1128$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
A. F. Bento, D. F. P. Leite, R. F. Claudino, D. B. Hara, P. C. Leal, and J. B. Calixto
The selective nonpeptide CXCR2 antagonist SB225002 ameliorates acute experimental colitis in mice
J. Leukoc. Biol., October 1, 2008; 84(4): 1213 - 1221.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
O. Sareila, M. Hamalainen, E. Nissinen, H. Kankaanranta, and E. Moilanen
Orazipone Inhibits Activation of Inflammatory Transcription Factors Nuclear Factor-{kappa}B and Signal Transducer and Activator of Transcription 1 and Decreases Inducible Nitric-Oxide Synthase Expression and Nitric Oxide Production in Response to Inflammatory Stimuli
J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 858 - 866.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. R. Ross, M. Kang, N. Shirwany, A. P. Malykhina, M. Drozd, and H. I. Akbarali
Nitrotyrosylation of Ca2+ Channels Prevents c-Src Kinase Regulation of Colonic Smooth Muscle Contractility in Experimental Colitis
J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 948 - 956.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Ziesche, M. Bachmann, H. Kleinert, J. Pfeilschifter, and H. Muhl
The Interleukin-22/STAT3 Pathway Potentiates Expression of Inducible Nitric-oxide Synthase in Human Colon Carcinoma Cells
J. Biol. Chem., June 1, 2007; 282(22): 16006 - 16015.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
A. Daddaoua, V. Puerta, P. Requena, A. Martinez-Ferez, E. Guadix, F. Sanchez de Medina, A. Zarzuelo, M. D. Suarez, J. J. Boza, and O. Martinez-Augustin
Goat Milk Oligosaccharides Are Anti-Inflammatory in Rats with Hapten-Induced Colitis
J. Nutr., March 1, 2006; 136(3): 672 - 676.
[Abstract] [Full Text] [PDF]

Home page
 J. Dent. Res.Home page
N. Kawashima, H. Nakano-Kawanishi, N. Suzuki, M. Takagi, and H. Suda
Effect of NOS Inhibitor on Cytokine and COX2 Expression in Rat Pulpitis
J. Dent. Res., August 1, 2005; 84(8): 762 - 767.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
V. Mollace, C. Muscoli, E. Masini, S. Cuzzocrea, and D. Salvemini
Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors
Pharmacol. Rev., June 1, 2005; 57(2): 217 - 252.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. P. Gobert, Y. Cheng, M. Akhtar, B. D. Mersey, D. R. Blumberg, R. K. Cross, R. Chaturvedi, C. B. Drachenberg, J.-L. Boucher, A. Hacker, et al.
Protective Role of Arginase in a Mouse Model of Colitis
J. Immunol., August 1, 2004; 173(3): 2109 - 2117.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2001 by the American Society for Pharmacology and Experimental Therapeutics.