Factor XIII A Activators

The first class of Factor XIII A activators are the compounds that enhance the functional activity of this protein through the cAMP-PKA pathway. This group includes adenosine, epinephrine, arachidonic acid, forskolin, alprostadil, iloprost, and isoproterenol. These compounds either directly or indirectly cause an increase in cAMP levels within the cell. For instance, adenosine, through the activation of A2a adenosine receptor, triggers cAMP production. Similarly, epinephrine binds to the β-adrenergic receptor, leading to a signaling cascade that increases cAMP levels. The elevated cAMP then activates protein kinase A (PKA), which is capable of phosphorylating Factor XIII A, therefore enhancing its functional activity.

The second class of Factor XIII A activators are those compounds that activate this protein via the PLC-Ca2+-calmodulin pathway. These include thrombin, ATP, histamine, bradykinin, and serotonin. These compounds activate different receptors, such as PAR1 (thrombin), P2Y1 (ATP), H1 (histamine), B2 (bradykinin), and 5-HT2 (serotonin). Activation of these receptors leads to the activation of phospholipase C (PLC), which increases intracellular Ca2+ levels. The rise in Ca2+ levels then activates calmodulin, which in turnactivates Factor XIII A, thereby enhancing its functional activity.