Tissue kallikrein synthesis and its modification by testosterone or low dietary sodium

Abstract

A method has been developed to measure the relative rate of rat tissue kallikrein synthesis which employs a specific antiserum raised against a purified rat urinary kallikrein. Incorporation of [35S]methionine into kallikrein and protein 20 min after intraperitoneal injection was measured in submaxillary gland, pancreas, kidney and descending colon. Kallikrein content was measured with a direct radioimmunoassay, and kallikrein-specific incorporation of [35S]methionine measured after immunoprecipitation. Kallikrein specific radioactivity (c.p.m./mg of enzyme) was about 100-fold greater than that in total protein in both kidney and colon. In contrast, in pancreas the incorporation into the enzyme was only 5-fold higher than into protein, and in submaxillary gland the incorporation was equivalent. Measured as kallikrein-specific radioactivity relative to total protein radioactivity incorporated in 20 min, kallikrein represents 0.18% of total protein synthesis in the kidney, 0.34% in the pancreas, 0.41% in the colon, but 7.29% in the submaxillary gland. Dietary Na+ restriction increased the relative rate of kallikrein synthesis 1.8-fold in the kidney without a comparable effect in submaxillary gland. In contrast, testosterone increased the relative rate of synthesis 2.3-fold in submaxillary gland, but decreased it in kidney. The data show that endogenous kallikrein synthesis differs markedly in various tissues, and that interventions which are known to change kallikrein content or excretion also change the relative rate of enzyme synthesis.

Renal Kallikrein and Hemodynamic Abnormalities of Diabetic Kidney

“…Because therapeutic doses of subcutaneously administered insulin may produce hyperinsulinemia (24), it is possible that insulin treatment contributed to the increase in renal and urinary kallikrein we observed in MD rats in this study. Whatever the cause, the rapid rate at which kallikrein turns over in the kidney strongly suggests that a sustained increase in excretion rate could not occur without increased kidney synthesis of kallikrein (25).…”

Abnormal regulation of renal kallikrein in experimental diabetes. Effects of insulin on prokallikrein synthesis and activation.

“…Amongst its effects on renal function, insulin increases sodium reabsorption by the distal tubule (37). It is possible that renal kallikrein could be involved in this action of insulin because states of sodium retention can be associated with raised renal kallikrein levels and synthesis ( 18,38), and kinin products of tissue kallikreins are potent stimuli to renal epithelial ion transport (9)(10)(11) worthy of note that when diabetic or normal rats were treated with insulin in our study, increases in renal kallikrein were accompanied by significant reductions in sodium excretion (data not shown).…”

Urinary Kallikrein Excretion in Normotensive Aging Female Rats

“…A low sodium diet increases both urinary and renal kallikrein (29) by stimulating the relative rate of synthesis (30). The level of urinary and renal kallikrein is also increased by mineralocorticoids and reduced by glucocorticoids (31) in male, but not in female rats, although no sex differences could be detected in the kallikrein level of untreated control animals (30). In male rats, testosterone exercises a permanent inhibitory control of the renal biosynthesis of kallikrein by altering mRNA accumulation (32).…”

“…Under normal conditions, tissue kallikrein contents exhibit dietary sodium, androgen, and sex-linked dependencies. A low sodium diet increases both urinary and renal kallikrein (29) by stimulating the relative rate of synthesis (30). The level of urinary and renal kallikrein is also increased by mineralocorticoids and reduced by glucocorticoids (31) in male, but not in female rats, although no sex differences could be detected in the kallikrein level of untreated control animals (30).…”