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)

Adrenaline alone did not induce aggregation of canine blood platelets in citrated plasma in vitro; however, it potentiated the aggregation caused by thrombin concentrations which are too low to induce coagulation. Simultaneous infusion of adrenaline and thrombin resulted in accumulation of 111In-labelled platelets in the lung and in the heart as measured by means of a gamma camera. Separately infused adrenaline or thrombin did not change the distribution of radioactivity. In vitro and in vivo hirudin and cyproheptadine inhibited the adrenaline-thrombin-induced platelet aggregation. Dihydroergotamine exerted no in vivo effect at the doses used.
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PMID:[Pharmacological investigations on the adrenalin-thrombin-induced platelet aggregation in dogs]. 248

Human platelet adenosine-3',5'-cyclic monophosphate (cAMP) levels were determined in platelet rich plasma (PRP) and in washed platelets by a modification of the protein binding assay; the validation of the method is described. Dihydroergotamine (DHE) inhibited epinephrine induced platelet aggregation (ID50 = 2.5 X 10(-7) mol/l), and increased cAMP levels in platelets by an alpha-adrenergic receptor blocking effect, since phentolamine but not propranolol, behaved similarly. The DHE induced cAMP accumulation was correlated to the inhibitory effect on aggregation and showed a characteristic alpha-adrenergic receptor pattern in the presence of alprostadil (PGE1) and epinephrine but not collagen or adenosine diphosphate (ADP). Thrombin induced aggregation was similarly affected by DHE but with 100 times higher concentration. Heparin was found to increase slightly ADP and epinephrine induced aggregation and to decrease cAMP. Also, heparin was found to inhibit thrombin induced platelet aggregation. In washed platelets, the inhibitory effect of thrombin on PGE1 induced cAMP accumulation was counteracted by heparin. This indicates that the binding site of thrombin on platelets is important in the control of adenyl cyclase. Evidence is presented that some of the beneficial synergistic effect of DHE and heparin may consist in the ability of those compounds to produce opposite effects on cAMP system in platelets.
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PMID:Effect of heparin and dihydroergotamine on platelet adenosine-3',5'-cyclic monophosphate. 282 55

The cause of postoperative DVT is considered to be changes in blood coagulation, stasis of blood within the veins, and injury to the vein wall. The coagulation changes have been investigated and documented and involve platelet activation, stimulation of the coagulation cascade, and blunting of endogenous fibrinolytic activity. Stasis has been objectively identified by retention of contrast material in soleal sinuses and marked changes in venous flow velocity in patients in the supine position and in those under general anesthesia. Vein wall injury is more controversial, but has been shown to be directly related to venodilation. Such dilation of veins occurs in response to operative trauma, hence venous endothelial damage most likely plays a part in the milieu responsible for postoperative DVT. The prophylaxis provided by the combination of dihydroergotamine and heparin appears to affect each of the three limbs of Virchow's triad. Heparin achieves its prophylactic benefit by activating antithrombin III. Activated antithrombin III affects numerous sites in the coagulation cascade. It has been shown that 1 micrograms of antithrombin III inhibits the formation of 1 unit of thrombin; however, in the presence of heparin, 1 micrograms of activated antithrombin III inhibits 750 units of thrombin. Dihydroergotamine increases venous smooth muscle tone without affecting arteriolar smooth muscle. Hence, it has the effect of preventing stasis without increasing blood pressure. It also affects the platelet membrane, prostaglandin synthesis, and blood distribution, although these findings need to be elucidated. The combination of dihydroergotamine and heparin seems to have a synergistic prophylactic effect in preventing postoperative DVT. Heparin modifies the coagulation changes, whereas dihydroergotamine minimizes stasis and potentially prevents the endothelial damage caused by excessive operative venodilation. Such a combination of effects can explain the synergistic prophylactic efficacy found when dihydroergotamine and heparin were employed in combination in the multicenter trial [42].
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PMID:Combined dihydroergotamine and heparin prophylaxis of postoperative deep vein thrombosis: proposed mechanism of action. 390 91