Abstract
Activation and aggregation of blood platelets is crucial for hemostasis and thrombosis. In the vascular system adenine nucleotides are important signaling molecules playing a key role in hemostasis. ADP was the first low molecular weight agent recognized to cause blood platelets activation and aggregation. NTPDases and adenylate kinase (AK) are the main enzymes involved in metabolism of extracellular adenine nucleotides. The majority of studies concentrated on the role of NTPDase1 (apyrase) in the inhibition of platelets aggregation. Up to now, there are still insufficient data concerning the role of AK in this process. We found that adenylate kinase activity in the serum of patients with myocardial infarction is significantly increased when compared to the healthy volunteers. The elevated activity of AK is connected to appearance of another isoform of that enzyme, expressed in patients with myocardial infarction. The influence of AK on the pig blood platelets aggregation induced by 20 μM ADP or 7.5 μg/ml rat collagen was examined. 1U of adenylate kinase added to platelet-rich plasma (PRP) before ADP or collagen, inhibited the platelets aggregation. One minute after induction of platelets activation by ADP as much as 5U of adenylate kinase was necessary to stop the platelet aggregation. In the case of collagen activated aggregation, only 2U of AK added 1 or 5 minutes after initiation of the aggregation process were sufficient for disaggregation of platelets. The increase of ATP: ADP ratio is probably responsible for the initiation of disaggregation process. We conclude that adenylate kinase is involved in regulation of plate-lets aggregation. Anticoagulative role of AK indicates the possibility of using this enzyme in the treatment of cardiovascular diseases.
Highlights
It is well known that platelets aggregation is the key process in thrombosis
Our experiments on the purine nucleotides metabolism in the human serum confirmed that adenylate kinase activity in patients with myocardial infarction is significantly increased when compared to the healthy volunteers (Figure 1)
We found that 20 μM ADP and 7.5 μg/ml rat collagen were used in further experiments as sufficient to the efficient aggregation of pig blood platelets
Summary
It is well known that platelets aggregation is the key process in thrombosis. The novel therapies against platelet-dependent thrombosis are targeted at purinergic receptor (P2Y12) activating the platelets aggregation. Adenine nucleotides play an important role in blood platelets function. Platelets possess three purinergic receptors for ecto-nucleotides: P2Y1 and P2Y12, which interact with ADP, and P2X1, which interacts with ATP [4,5,6]. The interaction of adenine nucleotides with their receptors activates platelets and leads to their aggregation. ADP is a key molecule involved in hemostasis and development of arterial thrombosis [7,8,9]. Activation of each of these nucleotide receptors results in unique signal transduction pathways that are important in the regulation of hemostasis and thrombosis [10]
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