Tissue kallikrein permits early renal adaptation to potassium load.
Tissue kallikrein (TK) is a serine protease synthetized in renal tubular cells located upstream from the collecting duct where renal potassium balance is regulated. Because secretion of TK is promoted by K+ intake, we hypothesized that this enzyme might regulate plasma K+ concentration ([K+]). We showed in wild-type mice that renal K+ and TK excretion increase in parallel after a single meal, representing an acute K+ load, whereas aldosterone secretion is not modified. Using aldosterone synthase-deficient mice, we confirmed that the control of TK secretion is aldosterone-independent. Mice with TK gene disruption (TK-/-) were used to assess the impact of the enzyme on plasma [K+]. A single large feeding did not lead to any significant change in plasma [K+] in TK+/+, whereas TK-/- mice became hyperkalemic. We next examined the impact of TK disruption on K+ transport in isolated cortical collecting ducts (CCDs) microperfused in vitro. We found that CCDs isolated from TK-/- mice exhibit net transepithelial K+ absorption because of abnormal activation of the colonic H+,K+-ATPase in the intercalated cells. Finally, in CCDs isolated from TK-/- mice and microperfused in vitro, the addition of TK to the perfusate but not to the peritubular bath caused a 70% inhibition of H+,K+-ATPase activity. In conclusion, we have identified the serine protease TK as a unique kalliuretic factor that protects against hyperkalemia after a dietary K+ load.
El Moghrabi
Soumaya
S
Faculté de Médecine, Université Paris-Descartes, Hopital Européen Georges Pompidou, Département de Physiologie, Assistance Publique-Hopitaux de Paris, F-75006 Paris, France.
Houillier
Pascal
P
Picard
Nicolas
N
Sohet
Fabien
F
Wootla
Bharath
B
Bloch-Faure
May
M
Leviel
Françoise
F
Cheval
Lydie
L
Frische
Sebastian
S
Meneton
Pierre
P
Eladari
Dominique
D
Chambrey
Régine
R
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000450:Aldosterone / Q000378:metabolism / Q000652:urine; D000818:Animals; D001692:Biological Transport; D019405:Cytochrome P-450 CYP11B2 / Q000172:deficiency / Q000235:genetics; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D017419:Potassium, Dietary / Q000008:administration & dosage; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism; D020840:Tissue Kallikreins / Q000235:genetics / Q000378:metabolism*
D017419:Potassium, Dietary; D000450:Aldosterone; D012964:Sodium; D019405:Cytochrome P-450 CYP11B2; D020840:Tissue Kallikreins; D017506:H(+)-K(+)-Exchanging ATPase; D011188:Potassium