Abstract
The calcium ion plays a critical role in vascular smooth muscle contraction and platelet activation as a second messenger [1]. Increase in the intracellular calcium ion concentration induced by various agonists is due to the release from intracellular calcium stores and/or influx of extracellular calcium ions (Fig. 1). It is generally accepted that intracellular calcium ion function in smooth muscle and nonmuscle cells is mostly regulated through calcium, calmodulin-dependent protein kinases and ultimate modulation of the extent of protein phosphorylation [2]. To investigate the molecular mechanisms involved in the calciumregulated system in smooth muscle cells and platelets, we developed selective inhibitors of each process of the calcium, calmodulin-dependent protein phosphorylation system [3]. The major mechanism for calcium activation of contractile proteins in vertebrate skeletal and cardiac muscle is a system consisting of calcium regulation ofthin filaments by troponin-tropomyosin [4]. However, contractile activity in smooth muscle and non muscle cells is thought to be primarily regulated by calcium, calmodulin-dependent myosin light-chain phosphorylation (Fig. 1) [5]. The biochemical processes of the calcium, calmodulin-dependent regulatory system in the microcirculation have though proved difficult to study. Here, we provide data on two selective inhibitors of myosin light-chain phosphorylation, which have different sites of action and are potent vasorelaxants and platelet inhibitors. These compounds are N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and 1-(5-chloronaphthalenesulfonyl)-1H-hexahydro-1, 4-diazepine (ML-9; Fig. 2).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have