The Hydrolysis of Biologically Active Peptides by Bovine Lung Tissue Factor (Thromboplastin) 1

Abstract

Summary

Tissue factor apoprotein and relipidated tissue factor preparations extensively hydrolyze bradykinin, Lys-bradykinin, Met-Lys-bradykinin, substance P, [Asp 1 ,Ile⁵-angiotensin II, [Asp 1 , Ile⁵]-angiotensin I, and human fibrinopeptide A while acting more slowly on [Sar 1 , Ile⁵]-angiotensin II, [Me₂Gly 1 , Ile⁵]-angiotensin II, bradykinin potentiating pentapeptide from B. jararaca, luteinizing hormone-releasing hormone, melanocyte stimulating hormone-release-inhibiting factor (Pro-Leu-Gly-NH₂), and oxytocin. No hydrolysis of thyro-tropin-releasing factor or bradykinin potentiating nonapeptide from B. jararaca is observed. Relipidated and apoprotein tissue factor act at identical rates under the conditions of the assay. Dansylation and chromatography of tissue factor-peptide incubation mixtures further indicate that relipidated and apoprotein tissue factor also hydrolyze peptides by identical mechanisms. No fewer than six bonds are hydrolyzed in bradykinin while the angiotensins and substance P are degraded to constituent amino acids. Only the N-terminal alanine is released from fibrinopeptide A. 2-Mercaptoethanol greatly inhibits the hydrolysis of bradykinin by relipidated tissue factor.

The authors are grateful to Dr. Maurice Manning of the Medical College of Ohio at Toledo for the generous gift of MIF, LH-RH, and oxytocin. They also thank Dr. M. C. Khosla of the Cleveland Clinic Foundation for his generous contribution of angiotensin II analogs.

This research was supported by a grant from the Northwest Ohio Chapter, Inc., of the American Heart Association.