Taurine and Its Derivatives: Analysis of the Inhibitory Effect on Platelet Function and Their Antithrombotic Potential

Abstract

Taurine is a semi-essential, the most abundant free amino acid in the human body, with a six times higher concentration in platelets than any other amino acid. It is highly beneficial for the organism, has many therapeutic actions, and is currently approved for heart failure treatment in Japan. Taurine has been repeatedly reported to elicit an inhibitory action on platelet activation and aggregation, sustained by in vivo, ex vivo, and in vitro animal and human studies. Taurine showed effectiveness in several pathologies involving thrombotic diathesis, such as diabetes, traumatic brain injury, acute ischemic stroke, and others. As human prospective studies on thrombosis outcome are very difficult to carry out, there is an obvious need to validate existing findings, and bring new compelling data about the mechanisms underlying taurine and derivatives antiplatelet action and their antithrombotic potential. Chloramine derivatives of taurine proved a higher stability and pronounced selectivity for platelet receptors, raising the assumption that they could represent future potential antithrombotic agents. Considering that taurine and its analogues display permissible side effects, along with the need of finding new, alternative antithrombotic drugs with minimal side effects and long-term action, the potential clinical relevance of this fascinating nutrient and its derivatives requires further consideration.

Keywords: coagulation; hemostasis/haemostasis; platelet activity; platelet aggregation; platelet reactivity; prothrombotic state; taurine; taurine derivatives/analogues; thrombosis; thrombotic diathesis.

Figure 1

Figure illustrating the influence of taurine and its derivatives (T) on various processes involved in platelet activation and aggregation. The proposed mechanisms of action (indicated by red arrows) are the following: 1. T inhibits platelet aggregation triggered by collagen, which is a strong platelet activator, but also an adhesion surface, being responsible for platelet adhesion (a); 2. T inhibits platelet activation and secretion (b) and consequently the process of platelet aggregation (c) by: (1) controlling intracellular calcium concentration-[Ca²⁺]_ic (limiting the calcium influx and suppressing the intraplatelet calcium (Ca²⁺) response to activating agonists); (2) down-regulating a growth modulator, β-thromboglobulin (β-TG) and adenosine triphosphate (ATP) release response to agonists, as markers of discharge from alpha and dense platelet granules; (3) decreasing the platelet cyclooxygenase activity and the platelet thromboxane A₂ (TxA₂) production; (4) suppressing platelet aggregation triggered by various agonists, such as adenosine diphosphate (ADP), thrombin, epinephrine, or platelet activation factor (PAF); (5) increasing of the endothelial nitric oxide (NO) release and prostacyclin (PgI₂) production and decreasing TxA₂ release. Other used abbreviations: GP—glycoprotein; vWF—von Willebrand factor; FBG—fibrinogen; PLC—phospholipase C; PIP₂ (membr)—phosphatidylinositol 4,5-bisphosphate from platelet plasmalemma; IP₃—inositol 1,4,5-trisphosphate; DAG—1,2-diacylglycerol; PKC—protein kinase C; DG—dense granule; AG—alfa-granule; 5-HT—5-hydroxytryptamine; PAF-R—PAF receptor; PAR_1,4—protease-activated receptor-1 and -4; P2Y₁—purinergic receptor 2Y₁; P2Y₁₂—purinergic receptor 2Y₁₂; IP—prostacyclin receptor; TP—TxA₂ receptor; α2 A-AR—alpha 2A adrenergic receptor; AC—adenylyl cyclase; cAMP—cyclic adenosine monophosphate; GC—guanylate cyclase; cGMP—cyclic guanosine monophosphate; PLA—phospholipase A; ArAc—arachidonic acid; COX—cyclooxygenase; PgG₂—prostaglandin G₂; PgH₂—prostaglandin H₂; (+) on the arrow represents up-regulation, (−) on the arrow represents down-regulation.