Inhibitory effects of sodium and other monovalent cations on purified versus membrane-bound kallikrein.

Glandular kallikrein is a serine proteinase implicated in epithelial ion transport processes. The present studies show that the enzymatic activities (alpha-N-tosyl-L-arginine methyl ester esterase and kininogenase) and the immunoreactivities of rat and human urinary kallikreins are inhibited by monovalent cations. The degree of inhibition, which exceeds 80% with physiological concentrations of cations, is dependent on temperature and preincubation time. The inhibitory effects are reversed when ions are removed via gel filtration. Bovine serum albumin or polyethylene glycol attenuate cationic inhibition, but sucrose or mannitol do not. Detergents, including deoxycholate, 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate, Triton X-100, and Lubrol PX also attenuate cationic inhibition of enzymatic activity or immunoreactivity. Membrane-bound kallikrein of renal cortical microsomal fractions or detergent-treated purified kallikrein lose less than 30% of their activity, even in the presence of 200 mM cation. These results show that both catalytic activity and immunoreactivity of purified versus membrane-bound kallikreins are affected, but to a different extent, by cations. The data suggest that monovalent cations may play a role in the regulation of soluble versus membrane-bound kallikrein activity.