Table 4.
Effect of KYNA on cellular processes
| Cellular process | Agent/factor | Cell type | Effect/comments | References |
|---|---|---|---|---|
| Receptor interaction | Glutamate receptors (NMDA, AMPA, kainate) | Hippocampal and cerebral cortical neurons, baby rat hemisected spinal cord | Antagonist | [64–66] |
| Alpha7 nicotinic receptor | Hippocampal neurons in cultures and in slices | Antagonist | [66] | |
| GPR35 | Chinese hamster ovary (CHO) cells transfected with human GPR35 | Agonist | [67] | |
| AhR | Human liver hepatocellular carcinoma (HepG2) | Agonist | [68] | |
| Rat basophilic leukaemia cell (RBL-2H3) | [69] | |||
| Transporter interaction | Multidrug resistance protein 4 (MRP4) | Human embryonic kidney cells (HEK293)—MRP4 over-expressing membrane vesicles; 0.1 mM KYNA | MRP4 substrate | [113] |
| Multidrug resistance protein 4 (MRP4) | Human embryonic kidney (HEK293) transduced with baculoviruses of human MRP4; membrane vesicle preparation | KYNA inhibited substrate-specific uptake by MRP4 in a concentration range of 0.1–1 mM | [114] | |
| Breast cancer resistance protein (BCRP) | Human embryonic kidney (HEK293) transduced with baculoviruses of human BCRP; membrane vesicle preparation | KYNA inhibited substrate-specific uptake by BCRP in a concentration range of 0.1–1 mM | ||
| Cell cycle regulation | p21Waf1/Cip1 | Human renal cell carcinoma Caki-2 | Gradually increased protein expression of p21Waf1/Cip1 (15 min–48 h of exposure to KYNA 2.5 mM) | [38] |
| Human colon adenocarcinoma HT-29 | KYNA 0.01–5 mM, dose-dependent increase of p21Waf1/Cip1 (4, 24 and 48 h exposure); no antiproliferative properties of KYNA in cells with silenced p21Waf1/Cip1 gene | [63] | ||
| pRb | Human renal cell carcinoma Caki-2 | Decreased phosphorylation (24 and 48 h exposure to KYNA 2.5 mM) | [38] | |
| Signal transmission | p38 MAPK | Human renal cell carcinoma Caki-2 | Decreased phosphorylation (15 min–48 h of exposure to KYNA 2.5 mM) | [38] |
| Human colon adenocarcinoma HT-29 | Gradually decreased phosphorylation (24 h exposure to KYNA 0.01–5 mM; 48 h exposure to KYNA 0.1–5 mM) | [99] | ||
| ERK1/2 | Human colon adenocarcinoma HT-29 | Decreased phosphorylation (4 h exposure to KYNA 5 mM; 24 h exposure to KYNA 0.01–5 mM) | [99] | |
| Akt | Human colon adenocarcinoma HT-29 | Decreased phosphorylation (4 h exposure to KYNA 1–5 mM; 24 h exposure to KYNA 1–5 mM; 48 h exposure to KYNA 0.1–5 mM) | [99] | |
| β-catenin | Human colon adenocarcinoma HT-29 | Increased expression after 24 and 48 h exposure to KYNA 5 mM | [99] |