RENAL ENZYMES THAT REGULATE BLOOD PRESSURE

对肾酶及其激活剂的研究

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.