Micromolar concentration of kynurenic acid in rat small intestine

Abstract

Kynurenic acid is an antagonist of glutamate and alpha-7 nicotinic acetylcholine receptors and an agonist of the G: -protein-coupled receptor GPR35, which is predominantly expressed in immune and gastrointestinal tissues. In this study, we report that kynurenic acid is present in the lumen of rat small intestine in micromolar concentration sufficient to affect the GPR35 receptor. Moreover, we show that kynurenic acid can be produced by Escherichia coli. We suggest that kynurenic acid may modulate gastrointestinal function and integrity.

International Union of Basic and Clinical Pharmacology. LXXXVIII. G Protein-Coupled Receptor List: Recommendations for New Pairings with Cognate Ligands

“…Wang et al (2006a) first reported that kynurenic acid (IUPHAR-DB ID no. 2918) was an agonist of GPR35; this observation has since been replicated in functional assays releasing interleukin 4 (Fallarini et al, 2010) and in a b-arrestin assay (Southern et al, 2013), but controversy remains whether the endogenous ligand reaches sufficient tissue concentrations to activate the receptor (Kuc et al, 2008). 2-Acyl lysophosphatidic acid (2-oleoyl-LPA; IUPHAR-DB ID no.…”

Kynurenic acid enhances expression of p21 Waf1/Cip1 in colon cancer HT-29 cells

“…Recently, it was also reported that KYNA is an agonist of aryl hydrocarbon receptor [2]. KYNA was found in human saliva [10], gastric juice, bile, pancreatic juice [15], mucus of rat small intestine [11] and mucus of pig colon [15]. Importantly, KYNA was also detected in several products of daily human diet and medicinal herbs [21,22].…”

“…Interestingly, previous studies indicated that the loss of the p21 gene and Western-style diet were additive on colon tumor formation in the murine model [27]. It should be emphasized that KYNA content found in mucus of rat ileum (0.003-0.016 mM) [11] and in mucus of pig colon (~0.0015 mM) [15] is high enough to influence expression of p21 Waf1/Cip1 and proliferation of HT-29 cells in vitro. Importantly, KYNA concentration in gastrointestinal tract may be easily increased.…”

Kynurenine pathway metabolism and the microbiota-gut-brain axis

“…They can also produce kynurenic acid which is present in rat small intestine at micromolar concentrations where it could activate the GPR35 receptor (Kuc et al, 2008). This is possibly due to the bacterial enzyme aspartate aminotransferase (AspAT) which is capable of the transamination of kynurenine and 3-HK to kynurenic acid (Han et al, 2001).…”