Plasma kallikrein-mediated activation of the renin-angiotensin system does not require prior acidification of prorenin
article
Activation of prorenin in the neutral phase afterpH 3.3 dialysis of human plasma depends on clotting factor XIIinitiatedprekallikrein to kallikrein conversion. Acid dialysis maybe necessary for destroying kallikrein inhibitors or renderingprorenin susceptible to attack by kallikrein. If the latter possibilityproves true, it is difficult to see how the factor XII-kallikrein pathway could activate prorenin in vivo. Plasma proreninwas therefore separated from active renin and from theprotease inhibitors α2-macroglobulin, Cl-inactivator, α1-antitrypsin,inter-α-trypsin inhibitor, and antithrombin III by gel filtration on Sephadex G-100 and affinity chromatography onBlue Sepharose CL-6B at neutral pH. The resulting proreninpreparation could be activated at pH 7.5 by highly purifiedhuman plasma kallikrein, which was prepared from prekallikreinby activation with active factor XII fragment β-factor XII a.Activation proceeded at 4 and 37 C at a kallikrein concentrationof 2 jug/ml, which is approximately 5% of the prekallikreinconcentration in normal plasma. It appears that an acid-inducedconformational change of the prorenin molecule is not requiredfor its activation by plasma kallikrein.
TNO Identifier
288104
Source
Journal of clinical endocrinology and metabolism, 54(2), pp. 343-348.
Pages
343-348
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