REGULATION OF RENIN PROCESSING AND SECRETION - CHEMIOSMOTIC CONTROL AND NOVEL SECRETORY PATHWAY

The renin-angiotensin-aldosterone system (RAAS) plays an important rol e in cardiovascular and electrolyte regulation in health and disease. Juxtaglomerular cells in the kidney regulate endocrine RAAS by physiol ogically controlling conversion of prorenin and secretion of renin. Th e classical baroceptor, neurogenic, and macula densa mechanisms regula te renin expression at the cellular level by Ca2+, adenosine 3',5'-cyc lic monophosphate (cAMP), and chemiosmotic forces (K+, Cl-, and water flux coupled to H+ movement). The baroceptor mechanism (through Ca2+) activates K+ and Cl- channels in the surface membrane and deactivates a KCl-H+ exchange chemisomotic transporter in the secretory granular m embrane. The neurogenic mechanism (through cAMP) promotes prorenin pro cessing to renin. The macula densa mechanism (through K+ and Cl-) invo lves the processing of prorenin to renin. Ca2+, by inhibiting the KCl- H+ exchange transporter, prevents secretory granules from engaging in chemiosmotically mediated exocytosis. cAMP, on the other hand, by stim ulating H+ influx, provides the acidic granular environment for proren in processing to renin. It is concluded that, in the presence of a fav orable chemiosmotic environment, prorenin is processed to renin, which may then be secreted by regulative degranulation or divergence transl ocation, a novel secretory pathway used by several secretory proteins, including renin.