The purine nucleoside adenosine, which is involved in several physiological functions, regulates a wide variety of immune and inflammatory responses and acts as modulator of gut functions. Although it is present at low concentrations in the extracellular space, stressful conditions, such as inflammation, can markedly increase its extracellular level up to micromolar range. Recent evidence suggests a prominent role of A2Areceptors (A2AR) and A2B receptors (A2BR) in the pathophysiology of inflammation (Sitkovsky and Lukashev 2005, Palmer and Trevethick 2008). In the current study we investigated the role of A2AR and A2BR to regulate contractility in untreated and inflamed rat colon preparations using specific receptor agonists and antagonists.<br>Inflammation was induced by intraluminal instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS, 0.01/0.1M, 30min). mRNA-expression was determined using RT-PCR. Contractions were measured isometrically in an organbath setup. All four adenosine receptor subtypes were expressed in untreated colon preparations. Activation of A1, A2B, and A3 receptor with specific agonists reduced the acetylcholine (ACh, 10?M)-induced contractions, while activation of A2BR enhanced. After incubation with TNBS morphologically damages in colonic mucosa and muscle walls were detectable followed by reduced ACh-contractions. The TNBS-mediated decrease of ACh-contractions as well as the morphological damages were partially normalized by co-incubation of TNBS with the A2AR agonist 2-p-[carboxyethyl]phenethylamino-5'-N-ethylcarboxamido-adenosine (CGS 21680, 10?M) or the A2BR antagonist 4-(2,3,6,7-tetrahydro-2,6-dioxo-1-propyl-1H-purin-8-yl-benzenesulfonic acid<br>(PSB 1115, 100?M).<br>In this study using an in-vitro inflammatory model, we demonstrate that the A2AR agonist CGS 21680 or the A2BR antagonist PSB 1115 effectively conteracted the development of TNBS-induced disturbances in colon preparations, so qualifying adenosine receptors as potential targets in colonic inflammation
