Early Acute Effects of Mercuric Chloride on Synthesis and Release of Kallikrein and on Distal Tubular Morphology of Rat Renal Cortical Slices

Abstract

The effect of mercuric chloride on kallikrein content and secretion of renal cortical slices was studied. Mercuric chloride showed dose-dependent inhibition of the secretion of immunoreactive and active kallikrein in the medium associated with a relative increase in the kallikrein tissue content of slices. However the net de novo biosynthesis was also reduced. Active and inactive kallikrein exhibited the same percentage of inhibition indicating that the activation mechanism of prokallikrein was not affected. These results suggest that mercuric chloride exerts an inhibition on tubular secretion but also on the tissular biosynthesis of kallikrein in these in vitro conditions. Morphological study of slices incubated in the presence of mercury also revealed significant tissular lesions which were located on the proximal tubule, but distal tubular changes were also observed. Distal nephrons were identified by the presence of immunoreactive kallikrein with the peroxidase-antiperoxidase method. These ultrastructural alterations included an increase in number and size of lysozomes, vacuoles and lipid droplets. These lesions were associated with an increased release of the lysozomal enzyme N-acetyl-beta-D-glucosaminidase. Since these distal tubular lesions are associated with inhibition of kallikrein secretion which is specifically located in the distal tubule, these results suggest that acute exposure of kidney cortical slices to mercuric chloride causes rapid and marked ultrastructural changes not only on the proximal tubule but also induced structural and biochemical effects at the distal tubule level. As incubation of mercuric chloride did not induce any direct alterations of immunoreactive and active kallikrein, it is likely that the observed inhibition of kallikrein synthesis and secretion are secondary to the morphological lesions.