Leukokinin-H generated from human ascites fluid; its isolation and pharmacology.

Abstract

Leukokinin-H, a pharmacologically active peptide, has been isolated from human ascites fluid following its generation in vitro at acid pH. The peptide has a molecular weight of approximately 2500. The partial sequence of Leu-Ala-Tyr-Thr — was obtained from the amino-terminal end. Arginine is the terminal amino acid at the carboxyl end. It was demonstrated that while cell-free ascites fluid generates leukokinin-H, the presence of neoplastic cells enhances the formation about 5 fold. A bradykinin-like peptide was formed in the fluid following storage at a low temperature of 4°C. The presence of neoplastic cells, however, did not enhance this peptide formation. Procedures are described for the isolation of leukokinin-H by chromatography. The peptide was clearly differentiated from bradykinin, Lys-bradykinin and Met-Lys-bradykinin by treatment of the leukokinin and other kinins with fluorescamine and separation of the fluorescamine peptides by gel electrophoresis. The pharmacology of leukokinin-H isolated from human ascites fluid is described and compared with bradykinin and leukokinins PMN and M. Like the other kinins, it is a potent agent in causing vascular permeability. Likewise it is a vasodepressor substance. Unlike bradykinin it has little spasmogenic activity on the guinea pig ileum. Its pharmacological properties as well as other evidence cited indicates that it may play an important role as a permeability factor in ascites fluid accumulation of neoplastic etiology.