Tissue kallikrein permits early renal adaptation to potassium load

• DOI: 10.1073/pnas.0913070107
• Publication Date: 2010-07-13T03:40:19Z
• Authors: Soumaya El Moghrabi; Pascal Houillier; Nicolas Picard; Fabien Sohet; Bharath Wootla; May Bloch-Faure; Françoise Leviel; Lydie Cheval; Sebastian Frische; Pierre Meneton; Dominique Eladari; Régine Chambrey
• Keywords: 0301 basic medicine; MESH: Hydrogen-Ion Concentration; MESH: Biological Transport; [SDV]Life Sciences [q-bio]; MESH: Tissue Kallikreins; In Vitro Techniques; Kidney; Aldosterone Synthase; MESH: Mice, Knockout; H(+)-K(+)-Exchanging ATPase; Mice; 03 medical and health sciences; MESH: Potassium, Dietary; MESH: Cytochrome P-450 CYP11B2; MESH: Reverse Transcriptase Polymerase Chain Reaction; MESH: Sodium; MESH: H(+)-K(+)-Exchanging ATPase; Animals; Cytochrome P-450 CYP11B2; MESH: Animals; Kidney Tubules, Collecting; MESH: Mice; MESH: Kidney Tubules, Collecting; Aldosterone; MESH: In Vitro Techniques; Mice, Knockout; Reverse Transcriptase Polymerase Chain Reaction; Sodium; MESH: Aldosterone; Potassium, Dietary; Biological Transport; MESH: Kidney; Hydrogen-Ion Concentration; MESH: Adaptation, Physiological; Adaptation, Physiological; [SDV] Life Sciences [q-bio]; MESH: Potassium; Potassium; Tissue Kallikreins

Tissue kallikrein (TK) is a serine protease synthetized in renal tubular cells located upstream from the collecting duct where potassium balance regulated. Because secretion of TK promoted by K + intake, we hypothesized that this enzyme might regulate plasma concentration ([K ]). We showed wild-type mice and excretion increase parallel after single meal, representing an acute load, whereas aldosterone not modified. Using synthase-deficient mice, confirmed control aldosterone-independent. Mice with gene disruption ( −/− ) were used to assess impact on [K ]. A large feeding did lead any significant change ] +/+ , became hyperkalemic. next examined transport isolated cortical ducts (CCDs) microperfused vitro. found CCDs exhibit net transepithelial absorption because abnormal activation colonic H ,K -ATPase intercalated cells. Finally, vitro, addition perfusate but peritubular bath caused 70% inhibition activity. In conclusion, have identified as unique kalliuretic factor protects against hyperkalemia dietary load.