Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat

Csaba Varga, Krisztina Horvath, Aniko Berko, Robin L. Thurmond, Paul J. Dunford, Brendan J.R. Whittle

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

The histamine H4 receptor is a G-protein coupled receptor with little homology to the pro-inflammatory histamine H1 receptor, expressed on cells of the immune system with hematopoietic lineage such as eosinophils and mast cells. The effects of the recently described highly selective histamine H4 receptor antagonists JNJ 10191584 and JNJ 7777120 have now been investigated on the acute colitis provoked by trinitrobenzene sulphonic acid over 3 days in the rat. Treatment with JNJ 10191584 (10-100 mg/kg p.o., b.i.d.) caused a dose-dependent reduction in macroscopic damage, inhibition of the TNBS-provoked elevation of both colonic myeloperoxidase and tumour necrosis factor-α (TNF-α), and a reduction in the histologically assessed increase in mucosal and submucosal thickness and neutrophil infiltration. JNJ 7777120 (100 mg/kg p.o., b.i.d.) likewise reduced the macroscopic injury and the increases in colonic myeloperoxidase and TNF-α levels. These findings indicate a pro-inflammatory role for the histamine H4 receptor in this model and suggest a novel pharmacological approach to the treatment of colitis.

Original languageEnglish
Pages (from-to)130-138
Number of pages9
JournalEuropean Journal of Pharmacology
Volume522
Issue number1-3
DOIs
Publication statusPublished - Oct 17 2005

Keywords

  • Colitis
  • Histamine H receptor antagonist
  • Inflammatory bowel disease
  • JNJ 10191584
  • JNJ 7777120
  • Neutrophil
  • Tumour necrosis factor-α

ASJC Scopus subject areas

  • Pharmacology

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