Cell experiment:

Pancreatic duct epithelial cells are treated with (0.1 μM-1 mM) uridine triphosphate. BrdU is added after different time points (12-24 hours). Proliferation is measured using the BrdU incorporation assay in triplicate[2].

Animal experiment:

Rats: Four main groups are tested: (1) sham without LAD ligation, (2) LAD ligation, (3) injected with UTP (0.44 μg/kg i.v.) 30 min before MI, (4) UTP injection (4.4 μg/kg i.v.) 24 h prior to MI. Several different concentrations of UTP are tested (0.044–44.4 μg/kg). Left ventricular systolic pressure (LVSP), end-diastolic pressure (LVEDP) and heart rates are monitored before, after UTP treatment and post MI[3].

Uridine triphosphate (UTP;Uridine 5'-triphosphate) is a pyrimidine nucleoside triphosphate that participates in glycogen metabolism and synthesis of RNA during transcription.

Uridine triphosphate treatment induces Schwannoma cell migration through activation of P2Y2 receptors and through the increase of extracellular matrix metalloproteinase-2 (MMP-2) activation and expression[1]. Uridine triphosphate-induced proliferation is mediated by protein kinase D, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, phosphatidylinositol 3-kinase (PI3K), Akt, and phospholipase D. Uridine triphosphate increases phosphorylation of Akt through protein kinase C, Src-family tyrosine kinase, Ca/calmodulin-dependent protein kinase II, and PI3K[2].

Uridine triphosphate reduces mitochondrial calcium levels following hypoxia. Early or late uridine triphosphate preconditioning is effective to reduce infarct size and superior myocardial function[3]. Uridine triphosphate treatment increases the number of monocytes and macrophages infiltrating the pouch and up-regulates the gene expression of IL-4 and IL-13 in the regional lymph nodes[4].

[1]. Lamarca A, et al. Uridine 5'-triphosphate promotes in vitro Schwannoma cell migration through matrix metalloproteinase-2 activation. PLoS One. 2014 Jun 6;9(6):e98998. [2]. Choi JH, et al. Uridine triphosphate increases proliferation of human cancerous pancreatic duct epithelial cells by activating P2Y2 receptor. Pancreas. 2013 May;42(4):680-6. [3]. Yitzhaki S, et al. Uridine-5'-triphosphate (UTP) reduces infarct size and improves rat heart function aftermyocardial infarct. Biochem Pharmacol. 2006 Oct 16;72(8):949-55. [4]. Iwaki Y, et al. Enhancement of antibody production against rabies virus by uridine 5'-triphosphate in mice. Microbes Infect. 2014 Mar;16(3):196-202.