ABSTRACT
The medicinal leech Hirudo medicinalis produces a low-molecular mass compound with properties similar to those of prostacyclin. It extracted with organic solvent, had affinity to 6-keto-PGF1alpha antibodies, inhibited human platelet aggregation induced in vitro by thrombin (by 50% at 4 pg/ml), and caused hypotension and secretion of plasminogen (t-PA) into the blood stream of rats. A main distinction from prostacyclin is stability of the substance due to covalent binding with the polypeptide chain of destabilase. Because of the high aggregability of destabilase, the molecules of the protein-lipid complex are organized into micelles that can change their spatial orientation depending on the nature of the solvent. Incorporation of hirudin and blood plasma kallikrein inhibitor into the micelle structure causes the formation of liposomes (with a molecular mass of the structural monomer 25 kDa). This complex with polypeptides provides not only stability but also rapid transmembrane penetration. The pure prostacyclin-like substance has a molecular mass of 391 Da and can be produced on destruction of the destabilase polypeptide chain.
Subject(s)
Epoprostenol/biosynthesis , Leeches/metabolism , Platelet Aggregation Inhibitors/metabolism , Animals , Blood Pressure/drug effects , Chromatography, Affinity , Electrophoresis, Polyacrylamide Gel , Epoprostenol/analogs & derivatives , Epoprostenol/isolation & purification , Epoprostenol/pharmacology , Humans , Liposomes , Male , Platelet Aggregation Inhibitors/isolation & purification , Platelet Aggregation Inhibitors/pharmacology , Rats , Rats, Inbred SHR , Rats, WistarABSTRACT
Medicinal leeches (Hirudo medicinalis) and the native secretion of their salivary glands diluted with saline (5 times) were successfully used for the treatment of some ear diseases: tinnitus caused by inner-ear affections, acute external otitis and chronic otitis media. The effect of diluted leech saliva injected into the region of the mastoid process by microelectrophoresis was 25-30% lower than that of the medicinal leeches.
