LEECH PROSTAGLANDINS AND THE ENZYME DESTAB ILASE AS THROMBOLYTIC AGENTS OF THE PREPARATIONS FROM THE MEDICINAL LEECHES

The thrombolytic effect of the leeching of thromboflebits has been well known from the ancient time. It is provided by the propertiesof the salivary gland secretion though leech saliva does not show proteolytic activity and does not activate plasminogen to plasmin. Butin leech saliva we have found the enzyme destabilase (isopeptidase-glutaminase) which hydrolyze the crosslinked fibrin. This mechanism can be the basis of a new type of fibrinolysis. We have observed the high affinity of destabilase to fibrin that provides the dissolutionof thrombous in circulating citrate blood in experiments in vitro. The high affinity of destabilase to fibrin correlates with its high ability to bound L-lysine, which inhibits isopeptidase and glutaminase activity of destabilase. Using radioimmunoassay for 6-keto-PgF₁ we have found prostaglandins in saliva and other preparations from the medicinal leeches:

3400 pg/ml of leech saliva

322 pg/mg of protein (the whole leeches extract)

351 pg/mg of protein (the head region extract)

63 pg/mg of protein (blood from the intestinal tract)

But the leech prostaglandins in contrast to 6-keto-PgF₁ has Strongly inhibited platelets aggregation stimulated by thrombin. The leech prostaglandins stimulate thrombolysis in rats after intravenous injection or oral administration. We have supposed that thrombolytic effect of leech prostaglandins is induced by the release of tissue plasminogen activator from vessel wall.

In the experiments on rats it has been shown that thrombolytic effect of leech saliva and preparations from the medicinal leeches is provided by the summary effect of the leech prostaglandins and the enzyme destabilase. After the extraction of prostaglandins by ethylacetate thrombolytic effect is diminished by 4O per cent.