Role of the A_2B receptor–adenosine deaminase complex in colonic dysmotility associated with bowel inflammation in rats

Abstract

BACKGROUND AND PURPOSEAdenosine A2B receptors regulate several physiological enteric functions. However, their role in the pathophysiology of intestinal dysmotility associated with inflammation has not been elucidated. Hence, we investigated the expression of A2B receptors in rat colon and their role in the control of cholinergic motility in the presence of bowel inflammation. EXPERIMENTAL APPROACHColitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS). Colonic A2B receptor expression and localization were examined by RT-PCR and immunofluorescence. The interaction between A2B receptors and adenosine deaminase was assayed by immunoprecipitation. The role of A2B receptors in the control of colonic motility was examined in functional experiments on longitudinal muscle preparations (LMPs). KEY RESULTSA2B receptor mRNA was present in colon from both normal and DNBS-treated rats but levels were increased in the latter. A2B receptors were predominantly located in the neuromuscular layer, but, in the presence of colitis, were increased mainly in longitudinal muscle. Functionally, the A2B receptor antagonist MRS 1754 enhanced both electrically-evoked and carbacholinduced cholinergic contractions in normal LMPs, but was less effective in inflamed tissues. The A2B receptor agonist NECA decreased colonic cholinergic motility, with increased efficacy in inflamed LMP. Immunoprecipitation and functional tests revealed a link between A2B receptors and adenosine deaminase, which colocalize in the neuromuscular compartment. CONCLUSIONS AND IMPLICATIONSUnder normal conditions, endogenous adenosine modulates colonic motility via A2B receptors located in the neuromuscular compartment. In the presence of colitis, this inhibitory control is impaired due to a link between A2B receptors and adenosine deaminase, which catabolizes adenosine, thus preventing A2B receptor activation. Abbreviations

Enteric Dysfunctions in Experimental Parkinsons Disease: Alterations of Excitatory Cholinergic Neurotransmission Regulating Colonic Motility in Rats

“…Contractile activity of colonic longitudinal and circular smooth muscle was recorded as previously described (Antonioli et al, 2014). After euthanization, the colon was removed and placed in cold Krebs' solution.…”

Protective Effects of Oxymatrine on Vascular Endothelial Cells from High-Glucose-Induced Cytotoxicity by Inhibiting the Expression of A2B Receptor

“…Studies in A 2B receptor knockout mice showed inhibition of the infiltration of neutrophils into tissues under hypoxic conditions [26,27]. Pro-inflammatory effects of A 2B receptors have been seen in murine lung inflammation models and in patients with asthma or chronic obstructive pulmonary disease, suggesting the potential therapeutic value of targeting A 2B receptors as an anti-inflammation measure to prevent the progression of these diseases [28,29]. It has been reported that the A 2B receptor may promote the expression and release of the inflammatory factor IL-6 by vascular endothelial cells in diabetes [12].…”

Aminophylline suppresses stress-induced visceral hypersensitivity and defecation in irritable bowel syndrome

“…Although previous studies have reported both positive and negative effects of adenosine on intestinal motility and nociception303132, the role of each AR subtype in IBS-D remains unknown. In an animal model of acute somatic pain (hot-plate test), an antagonist of A 2B ARs but not of A 1 ARs or A 2A ARs showed an analgesic effect31, whereas in another animal model of somatic pain (formalin test), an A 2A AR antagonist acted as an analgesic3033.…”

“…In an animal model of acute somatic pain (hot-plate test), an antagonist of A 2B ARs but not of A 1 ARs or A 2A ARs showed an analgesic effect31, whereas in another animal model of somatic pain (formalin test), an A 2A AR antagonist acted as an analgesic3033. A 2B AR-knockout mice have been reported to exhibit decreased stool frequency32 whereas an A 2B AR antagonist enhanced colonic contraction in rats30.…”