The Renin-Angiotensin-Aldosterone system plays a major role in the regulation of both salt and fluid homeostasis of the body. The regulation and the mechanism of renin secretion from the juxtaglomerular epithelioid cells (JG-cells) of the kidney have been considered for long. The detailed secretion mechanisms of the JG-cells, however, are still unknown. We have therefore analyzed by 3-dimensional reconstructions made out of serial TEM-images the morphology and exocytoses of renin containing vesicles of mouse kidneys with both nonstimulated and stimulated renin secretion.

Reconstructions of nonstimulated cells and cells with stimulated secretion revealed numerous renin containing vesicles which appeared either as small single granules or as irregularly shaped and connected to each other, forming interconnected cavern like structures. Stimulation of renin secretion with isoproterenol and the calcium chelator EGTA was associated with intracellular fusion of vesicles. In addition, during strong stimulation of renin secretion, exocytotic events such as contacts of vesicles with the cell membrane became visible. We speculate that an intracellular fusion of renin containing vesicles is required for the release of renin stored in the interior of the cell. In addition, we have analyzed 3-D reconstructions of nonstimulated and stimulated JG-cells of C57BL/6J-Lystbg-J/J-mice (beige-mice). These mice lack a functional lysosomal trafficking protein (lyst), which plays an important role for the correct formation and fragmentation of lysosomal and secretory organelles. Lack of lyst proteins results in significantly enlarged lysosomal and secretory organelles in many cell types. In JG-cells of stimulated and nonstimulated beige mice, the renin containing vesicles were significantly enlarged and of abnormal morphology. Each JG-cell contained a small number of very large vesicles with irregular and/or pancake-like shape. There was no difference regarding the morphology of the renin containing vesicles between nonstimulated and stimulated beige cells. In stimulated JG cell of beige-cells, exocytotic events became visible. These findings suggest indicate that fusion of renin storage vesicles with the cell membrane is not restricted to smaller vesicles but also occurs in very large renin containing vesicles of the beige-mouse.

The sum of our findings suggest that renin is secreted from JG cells by a mechanism similar to "compound-exocytosis".