Urinary kallikrein: a physiological regulator of epithelial Na+ absorption

Abstract

The apical membrane of the mammalian urinary bladder contains two populations of ionic conductances--one Na+ selective and amiloride blockable, the other cation selective and amiloride insensitive (a leak channel). Addition of kallikrein (an enzyme of unknown function normally found in urine) to the mucosal solution of the mammalian urinary bladder epithelium resulted in the loss (over a 2-hr period) of amiloride-sensitive Na+ current and an increase in the leak current that is amiloride insensitive. The rate of hydrolysis of Na+ channels is a first-order process that is concentration (activity) dependent and described by simple Michaelis-Menten kinetics with a maximum rate of 9.5 X 10(-3) min-1. At the activities measured in human urine, the corresponding rate constant will decrease Na+ channel density by 99.5% in 24 hr. Amiloride protects the amiloride-sensitive Na+ channels from degradation but not the leak pathway. The rate of hydrolysis of the leak pathway as well as the kinetics of hydrolysis are the same as that described for the Na+ channel. Of interest is that the leak pathway is hydrolyzed into a form that seems to partition between the apical membrane and mucosal solution (an unstable leak pathway). These results and previous findings suggest a regulatory role for kallikrein in salt and water homeostasis.