INFLUENCE OF METALS ON THE ACTIVITY OF A BRADYKININ-DESTROYING ENZYME KININASE

Journal/Book: Brit. J. Pharmacol. (1962) 19 442-450. 1962;

Abstract: From the Pharmacotherapeutic Laboratory University of Amsterdam Received July 20 1962 Kininase prepared from guinea-pig serum was inhibited by cysteine at pH 7.4 to 7.6. A similar effect was found with edetic acid. The enzyme blocked by edetic acid was reactivated immediately by addition of Mn++ Co++ and Zn++. These findings indicate that kininase is a metal-activated enzyme. Rocha e Silva Beraldo & Rosenfeld (1949) found in their experiments an formation of bradykinin by trypsin and snake venoms that the activity was rapidly destroyed an further incubation ; this destruction could be prevented by cysteine hydrochloride (Frey Kraut & Werle 1950 ; Rocha e Silva 1955). It was suggested that cysteine hydrochloride inhibits the kininase of serum and kidney. Lewis (1960) reported that cysteine also potentiates the smooth muscle stimulating action of plasma kinin. This was confirmed by Picarelli Henriques & Oliveira (1962) who ascribed this potentiating effect of cysteine to inactivation of the kininase present in the test Organs. However it is possible that cysteine hydrochloride as a strongly acid compound not only inhibits the kininase activity but also interferes with the smooth muscle stimulating action of plasma kinin by dranging the pH of the medium. Besides cysteine may inactivate kininase by binding divalent metal ions for Smith (1951) found that several peptidases in crude tissue extracts are specifically inactivated by cysteine cyanide and sulphide compounds which strongly and specifically bind divalent metal ions. Since the last possibility seemed to us most likely we studied the influence of neutralized solutions of cysteine hydrochloride an kininase activity thus excluding any effect that lowering the pH of the medium might have an the activity of this enzyme or an smooth muscle. ... ___MH

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