Effects of uridine and nucleotides on hemostasis parameters

Uridine, a pyrimidine nucleoside, may be present in the body in free form or in phosphated forms of nucleotides. Uridine enters the structure of nucleotide sugars and the structure of nucleic acids. It is involved in many physiological functions such as glycogen biosynthesis, protein and lipid glycolization. The uridine nucleotides exert their cellular effects through purinergic receptors. Hemostasis is a physiological system that functions to prevent the blood that should be present in the circulatory system from going out of the system and to stop the bleeding in case of any damage. It can be life-saving by preventing blood loss, and can lead to life-threatening consequences with abnormal hemostasis in the vascular bed. Several subtypes of purinergic receptors have been identified on platelets. Although there are detailed studies on the effects of adenine and nucletides on platelets, these studies on uridine and nucleotides are limited. In this study, the effects of uridine and nucleotides on hemostasis parameters were investigated at cellular level by optical aggregometer, and at system level by thromboelastogram. In the aggregometer experiments, the final concentrations of uridine 10, 100 and 1000 M and final concentrations of 1, 10, 50, 100, 500 and 1000 M of UMP, UDP and UTP were studied. Uridine or nucleotide was added to the platelet-rich plasma and incubated for 3 minutes. Then, aggregation curves obtained by stimulating aggregation with ADP, collagen or epinephrine were compared according to the control group. In thromboelastogram experiments, final concentrations of 1000 M of uridine and nucleotides were studied. Thromboelastogram parameters were evaluated according to the control group. In the aggregometer, uridine was found to activate low concentration collagen-induced aggregation, UDP and especially UTP inhibited ADP and collagen-induced aggregation, depending on the concentration. UDP and UTP showed low concentrations of activation and high concentrations of inhibition in epinephrine-induced aggregations. While thromboelastogram showed no effect of uridine and UMP, hypercoagulant effect of UDP and hypocoagulant effect of UTP were observed. The ineffectiveness of UMP, the observation of the effects of UDP and especially UTP with increasing concentration suggest that inhibitory effects on platelets are related to phosphate groups. The inhibitory effect of UTP was also observed by thromboelastogram. The effects of UDP on activation in thromboelastogram are opposite and first-time findings compared to UTP.