Adenosine can show anti-inflammatory as well as pro-inflammatory activities. The contribution of the specific
adenosine receptor subtypes in various cells, tissues and organs is complex. In this study, we examined the effect of the
adenosine A(2A) receptor agonist
CGS 21680 and the A(2B)R antagonist
PSB-1115 on acute
inflammation induced experimentally by 2,4,6-trinitrobenzenesulfonic
acid (TNBS) on rat ileum/jejunum preparations. Pre-incubation of the ileum/jejunum segments with TNBS for 30 min resulted in a concentration-dependent inhibition of
acetylcholine (ACh)-induced contractions. Pharmacological activation of the A(2A)R with
CGS 21680 (0.1-10 microM) pre-incubated simultaneously with TNBS (10 mM) prevented concentration-dependently the TNBS-induced inhibition of the ACh contractions. Stimulation of A(2B)R with the selective agonist
BAY 60-6583 (10 microM) did neither result in an increase nor in a further decrease of ACh-induced contractions compared to the TNBS-induced inhibition. The simultaneous pre-incubation of the ileum/jejunum segments with TNBS (10 mM) and the selective A(2B)R antagonist
PSB-1115 (100 microM) inhibited the contraction-decreasing effect of TNBS. The effects of the A(2A)R agonist and the A(2B)R antagonist were in the same range as the effect induced by 1 microM
methotrexate. The combination of the A(2A)R agonist
CGS 21680 and the A(2B)R antagonist
PSB-1115 at subthreshold concentrations of both agents found a significant amelioration of the TNBS-diminished contractility. Our results demonstrate that the activation of A(2A) receptors or the blockade of the A(2B) receptors can prevent the
inflammation-induced disturbance of the ACh-induced contraction in TNBS pre-treated small intestinal preparations. The combination of both may be useful for the treatment of
inflammatory bowel diseases.