gms | German Medical Science

The purine nucleoside adenosine regulates inflammatory responses and acts as a modulator of gut functions. By activation of different receptor subtypes adenosine is able to induce anti-inflammatory or pro-inflammatory impacts.

This study was aimed to investigate the role of A2A and A2B receptors to influence the morphology and contractility in inflamed rat colon preparations as well as the involvement of A2A receptors in the TNF-α pathway and its influence by STW 5 (Iberogast®) and STW 6 (Iberis amara) using specific receptor agonists/antagonists. Inflammation was induced by intraluminal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Contractions were measured isometrically in an organ bath set up. Gene expression was determined using RT-PCR. Radio ligand binding assays were carried out with rat brain homogenates. Morphological changes were estimated after van Gieson staining.

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, 10µM)-induced contractions, while activation of A2BR enhanced it. After incubation with TNBS morphological 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 is partially normalized by co-incubation of TNBS with CGS 21680 (10µM) or with PSB 1115 (100µM). These results are in accordance with ligand binding studies indicating that STW 5 but not STW 6 interact with the A2AR and decreased the TNF-α gene expression and release.

Anti-inflammatory mechanisms and cell protective actions of STW 5 are partly due to the interaction with adenosine receptors. The results give a clear-cut correlation with symptom improvements in clinical trials and thereby highlight the relevance of STW 5 as a therapeutic approach in IBS.