High concentration of kynurenic acid in bile and pancreatic juice

Abstract

Kynurenic acid (KYNA) is an agonist of the G-protein-coupled receptor GPR35, which is predominantly expressed in gastrointestinal tissues. The aim of this study was to determine the content of KYNA in gastric juice, bile and pancreatic juice and intestinal content. KYNA was determined by means of high performance liquid chromatography. The mean concentrations of KYNA in human gastric juice is 9.91 +/- 0.71 nM in contrast to human bile (832.5 +/- 204.1 and 306.8 +/- 35.2 nM) obtained from patients with cholecystolithiasis and obstructive jaundice, respectively. In pigs, the KYNA levels in bile and pancreatic juice are 1,113.3 +/- 63.34 and 757.0 +/- 394.4 nM, respectively. The KYNA concentration increases along the digestive system, reaching 1,638 nM in the colon content. We suggest that the liver and pancreas affect the content of kynurenic acid in the lumen of the digestive tract.

Kynurenic acid inhibits colon cancer proliferation in vitro: effects on signaling pathways

“…However, KYNA was also found in physiological fluids in gastrointestinal tract: human saliva (Kuc et al 2006), gastric juice, bile, pancreatic juice (Paluszkiewicz et al 2009), mucus of rat small intestine (Kuc et al 2008) as well as mucus of pig (Paluszkiewicz et al 2009) and human colon (Walczak et al 2011). KYNA may affect several various cellular processes as it is also present in several products of human diet (Turski et al 2009, 2011) and it is absorbed after intragastric administration into the bloodstream and transported to peripheral organs (Turski et al 2009).…”

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.…”

Effect of dietary administration of kynurenic acid on the activity of splenocytes of the rainbow trout (Oncorhynchus mykiss)

“…Apart from immune cells, GPR35 receptors are also present on the surface of enterocytes in intestinal crypts, which may imply some involvement of KYNA in the local immunologic response in the digestive tract and in the functions performed by enterocytes. Until today, it has been confirmed that kynurenic acid affects the mitotic activity and differentiation of the epithelium of the digestive tract and that it can protect against ulceration or other damage of mucus membranes in the digestive system or even -to some extent -against intoxication [6]. It is also known that KYNA is effectively absorbed in the digestive Effect of dietary administration of kynurenic acid on the activity of splenocytes of the rainbow trout (Oncorhynchus mykiss) tract [7], which, in combination with its ability to affect the immune system, stimulates research on using KYNA as a natural immunomodulator in prophylaxis and therapy of infectious and inflammatory diseases.…”