Abstract
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder, with the characteristic symptoms of chronic abdominal pain and altered bowel habits (diarrhea, constipation, or both). IBS is a highly prevalent condition, which negatively affects quality of life and is a significant burden on global healthcare costs. Although many pharmacological medicines have been proposed to treat IBS, including those targeting receptors, channels, and chemical mediators related to visceral hypersensitivity, successful pharmacotherapy for the disease has not been established. Visceral hypersensitivity plays an important role in IBS pathogenesis. Immune activation is observed in diarrhea-predominant patients with IBS and contributes to the development of visceral hypersensitivity. Adenosine is a chemical mediator that regulates many physiological processes, including inflammation and nociception. Among its receptors, the adenosine A2B receptor regulates intestinal secretion, motor function, and the immune response. We recently demonstrated that the adenosine A2B receptor is involved in visceral hypersensitivity in animal models of IBS. In this review, we discuss the possibility of the adenosine A2B receptor as a novel therapeutic target for IBS.
Highlights
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder involving abdominal pain or discomfort, bloating, diarrhea, and/or constipation [1]
These findings demonstrate that immune activation in patients with IBS is associated with clinical outcomes, and that anti-inflammatory agents can be effective in the treatment of IBS
We have described the anti-inflammatory actions of the A2B receptor, it is difficult to reconcile the evidence into either pro-inflammatory or anti-inflammatory roles for the receptor, as A2B receptor knockout mice appear to have a pro-inflammatory phenotype compared to wild-type controls, characterized by elevated plasma tumor necrosis factor (TNF)-α levels and increased vascular permeability for albumin in the colon, kidneys, and lungs [55]
Summary
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder involving abdominal pain or discomfort, bloating, diarrhea, and/or constipation [1]. Pharmacological treatments effective against abdominal pain are insufficient in IBS-D therapy, and drugs targeting chemical mediators or receptors involved in visceral sensitivity have recently been developed. Alosetron and ramosetron, both antagonists of the serotonin 3 (5-hydroxytryptamine 3; 5-HT3) receptors, are approved for use in patients with IBS [5,6]. Immune activation in the gastrointestinal tract has recently attracted much attention as a potential mechanism This is because inflammatory mediators in the intestinal mucosa, such as adenosine 5 -triphosphate (ATP), bradykinin, and adenosine, activate primary afferent nerve endings. We focus on the role of the A2B receptor in gut function and the immune response, and its involvement in IBS pathogenesis, in the control of intestinal secretion, motility, and sensation
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