Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombin contributes to hemostasis by activating platelets, the formation of fibrin, and contraction of the injured vessel. These effects are mediated through the proteolytic activity of thrombin. We hypothesized that thrombin may have a role in vasospasm after arterial injury and examined the physiologic and cellular signaling events of thrombin in intact vascular smooth muscles. Thrombin stimulation of strips of bovine carotid artery smooth muscle led to contractions which relaxed with the addition of the nitric oxide donor, sodium nitroprusside. However, washout of the thrombin and SNP resulted in the re-generation of force. This was not observed with other agonists such as endothelin, thromboxane analogues, or serotonin. Using two-dimensional immunoblotting we demonstrate that thrombin stimulation leads to increases in the tyrosine phosphorylation of 4 proteins, three different isoforms of P44 mitogen activated protein kinase (MAPK) and one isoform of P38 stress activated protein kinase (SAPK). Activation of P38 SAPK leads to activation of MAPKAP kinase-2 and a major substrate protein of MAPKAP kinase-2 is the small heat shock protein, HSP27. HSP27 has been implicated in mediating smooth muscle contraction. These data suggest that in the setting of arterial injury, thrombin-induced contraction may supercede over short acting vasorelaxants such as NO resulting in vasospasm. In addition to stress, physiologic substances such as thrombin, activate SAPKs leading to increases in the phosphorylation of HSP27. Thus, thrombin may play a central role in hemostasis after vascular injury and in the pathologic responses to plaque rupture and thrombosis in atherosclerosis.
 ...
PMID:Thrombin contraction of vascular smooth muscle: implications for vasospasm. 1277 50

Thrombin mediates the life-threatening cerebral edema and blood-brain barrier (BBB) damage that occurs after intracerebral hemorrhage (ICH). We previously found that the selective cannabinoid receptor 2 (CB2R) agonist JWH-133 reduced brain edema and neurological deficits following germinal matrix hemorrhage (GMH). We explored whether CB2R stimulation ameliorated thrombin-induced brain edema and BBB permeability as well as the possible molecular mechanism involved. A total of 144 Sprague-Dawley (S-D) rats received a thrombin (20 U) injection in the right basal ganglia. JWH-133 (1.5 mg/kg) or SR-144528 (3.0 mg/kg) and vehicle were intraperitoneally (i.p.) injected 1 h after surgery. Brain water content measurement, Evans blue (EB) extravasation, Western blot, and immunofluorescence were used to study the effects of a CB2R agonist 24 h after surgery. The results demonstrated that JWH-133 administration significantly decreased thrombin-induced brain edema and reduced the number of Iba-1-positive microglia. JWH-133 also decreased the number of P44/P42(+)/Iba-1(+) microglia, lowered Evans blue extravasation, and inhibited the elevated matrix metallopeptidase (MMP)-9 and matrix metallopeptidase (MMP)-12 activities. However, a selective CB2R antagonist (SR-144528) reversed these effects. We demonstrated that CB2R stimulation reduced thrombin-induced brain edema and alleviated BBB damage. We also found that matrix metalloproteinase suppression may be partially involved in these processes.
 ...
PMID:A Cannabinoid Receptor 2 Agonist Prevents Thrombin-Induced Blood-Brain Barrier Damage via the Inhibition of Microglial Activation and Matrix Metalloproteinase Expression in Rats. 2637 16