The adenosine A2A receptor agonist CGS 21680 fails to ameliorate the course of dextran sulphate-induced colitis in mice

Inflamm Res. 2007 May;56(5):204-9. doi: 10.1007/s00011-006-6150-7.

Abstract

Objective: In this study we investigated the effect of CGS 21680 (2-p-(2-Carboxyethyl)phenethylamino-5-N-ethylcarboxamidoadenosine hydrochloride), an adenosine A2A receptor agonist, in a model of dextran sulphate sodium (DSS)-induced colitis.

Methods: NMRI mice were fed 5 % (w/v) DSS, and were treated intraperitoneally with 0.5 mg/kg CGS 21680 or vehicle for 10 days. Changes of bodyweight, colon length, the incidence of rectal bleeding, levels of macrophage inflammatory protein (MIP)-1alpha, MIP-2, interferon gamma, interleukin (IL)-1beta, IL-12 and tumour necrosis factor-alpha from homogenates of colon biopsies, and the release of [3H]acetylcholine (ACh) from longitudinal muscle strip were determined.

Results: DSS significantly decreased bodyweight, colon length, and it increased the incidence of rectal bleeding and levels of MIP-1alpha, MIP-2 and IL-1beta compared to DSS-untreated animals. CGS 21680 had no effect on these changes. No change could be observed in release of ACh in DSS-induced colitis with or without CGS 21680.

Conclusion: In summary, CGS 21680 is ineffective in ameliorating DSS-induced colitis in mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / genetics
  • Acetylcholine / metabolism
  • Adenosine / analogs & derivatives*
  • Adenosine / therapeutic use
  • Adenosine A2 Receptor Agonists*
  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CXCL2
  • Chemokines / genetics
  • Chemokines / metabolism
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Dextran Sulfate
  • Gene Expression Regulation / drug effects
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Macrophage Inflammatory Proteins / genetics
  • Macrophage Inflammatory Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains / physiology
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology
  • Phenethylamines / therapeutic use*

Substances

  • Adenosine A2 Receptor Agonists
  • Antihypertensive Agents
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • Interleukin-1beta
  • Macrophage Inflammatory Proteins
  • Phenethylamines
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Dextran Sulfate
  • Adenosine
  • Acetylcholine