title: Direct action of kallikrein and other proteases on the renin-angiotensin system.
abstract: Kallikrein is present in the renal tubule near the macula densa, and it has recently been shown to activate inactive renin in human plasma. We recently showed that kallikrein was a potent stimulus of renin release and increased renin secretion in a dose-dependent fashion. To study its effect on renal renin release, we superfused rat renal cortical slices with purified rat urinary kallikrein. Kallikrein-stimulated renin release was completely abolished by trasylol and by amiloride, but was not affected by soybean trypsin inhibitor. Indomethacin did not block kallikrein action, indicating that kallikrein's effect is not mediated via kinin generation and prostaglandins. Kallikrein-stimulated renin release was not blocked by propranolol, trasylol did not block isoproterenol, and dibutyryl cyclic AMP stimulated renin release, indicating that kallikrein may not play a role in the beta-adrenergic mechanism of renin release. There was no demonstrable acid-activatable or kallikrein activatable renin in the superfusate, suggesting that all of the renin release was in the active form. Cathepsin D and plasmin also stimulated renin release from kidney slices in pH 6.0 buffer, whereas trypsin and pepsin did not. Our results support the hypothesis that kallikrein may play a role in the secretion of renin by the kidney. Other proteases can also release renin from the kidney.
mesh_terms: D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D066298:In Vitro Techniques; D007610:Kallikreins / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D010447:Peptide Hydrolases / Q000494:pharmacology*; D051381:Rats; D012083:Renin / Q000378:metabolism*
chemical_list: D000809:Angiotensins; D010447:Peptide Hydrolases; D007610:Kallikreins; D012083:Renin