Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 7 (4), 655-65

Inhibition of Cathepsin D-type Proteinase of Macrophages by Pepstatin, a Specific Pepsin Inhibitor, and Other Substances

Inhibition of Cathepsin D-type Proteinase of Macrophages by Pepstatin, a Specific Pepsin Inhibitor, and Other Substances

M H McAdoo et al. Infect Immun.

Abstract

The macrophage is the main cell participating in chronic inflammation. It contains an acid-acting, cathepsin D-type proteinase with the specificity of pepsin, which may release mediators of the inflammatory process. To find new pharmaceutical inhibitors of this proteinase, we tested a variety of chemical compounds in vitro. For this survey, the possible inhibitor (at a concentration of 0.4 mg/ml) was assayed with partially purified cathepsin D-type proteinase from beef lung (a macrophage-rich tissue) and hemoglobin as the substrate. Diazophenylbutanone, three acetophenones, two barbiturates, a gold salt, a copper chelate of a substituted nicotinic acid, a hexapeptide containing a d-amino acid, and Pepstatin inhibited this enzyme; over 200 other potential inhibitors did not. By far the most active and specific inhibitor found to date is Pepstatin, a pentapeptide with two gamma-NH linkages, two beta-OH groups, and five branched aliphatic side chains. Banyu Pharmaceutical Co., Tokyo, Japan, produces this nontoxic compound for the treatment of peptic ulcers. In vitro, as little as 4 ng of Pepstatin inhibits the acid-acting cathepsin D-type proteinase purified from beef and rabbit lung as well as the similar proteinase of rabbit peritoneal and pulmonary macrophages.

Similar articles

See all similar articles

Cited by 6 articles

See all "Cited by" articles

References

    1. Immunology. 1969 Sep;17(3):421-8 - PubMed
    1. J Biol Chem. 1968 May 25;243(10):2821-8 - PubMed
    1. Biochemistry. 1969 Oct;8(10):4183-90 - PubMed
    1. Biochem J. 1959 Sep;73:33-41 - PubMed
    1. Science. 1972 Feb 11;175(4022):656 - PubMed

MeSH terms

LinkOut - more resources

Feedback