Protein Kinase, cGMP Dependent Type I (PRKG1)

Two main forms of cGK have been identified: a soluble form designated type I and an intrinsic membrane-bound form designated type II.Prkg1 knockout mice showed impaired platelet responses to VWF or low doses of thrombin and prolonged bleeding time. Human platelet aggregation induced by VWF or low-dose thrombin was inhibited by PRKG1 inhibitors but enhanced by cGMP. Furthermore, a cGMP-enhancing agent, sildenafil, promoted VWF- or thrombin-induced platelet aggregation. The cGMP-stimulated platelet responses were biphasic, consisting of an initial transient stimulatory response that promoted platelet aggregation and a subsequent inhibitory response that limited the size of thrombi.