The investigations of renal enzymes and their activators will be continued with emphasis on tissue kallikrein and renin. Although these enzymes are concentrated in the kidney, they are present in other organs as well. The recent developments in deciphering the structure of pro-renin and prokallikrein make it possible to establish the mode of activation and identify endogenous activating enzymes of the inactive pro-enzymes. The activation of both homogeneous prokallikrein and prokallikrein hound to cell membranes will be studied. With purified prokallikrein, activation will be correlated with the N-terminal sequence in order to determine how the removal of one or more N-terminal amino acids during activation could affect enzymatic activity and antigenicity. The subcellular site of activation of prokallikrein will be localized by adopting a novel technique combining immunohistochemistry with ultra- structural studies. The search for endogenous tissue activating enzymes for both prokallikrein and prorenin will continue. The site of activation in the peptide chain of prorenin and the resulting N-terminal sequence of the enzyme will be characterized. The length of the N-terminal propeptide residue still present after the activation will be correlated with the renin activity. The studies on the activation of prokallikrein and prorenin will bring about a better understanding of the two frequently oppositely acting systems, which can control normal and abnormal blood pressure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL036081-06
Application #
3350701
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1989-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
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