Tissue kallikrein-deficient mice display a defect in renal tubular calcium absorption.
Renal tubular calcium (RTCa) transport is one of the main factors that determine serum Ca concentration and urinary Ca excretion. The distal convoluted and connecting tubules reabsorb a significant fraction (10%) of filtered Ca. These tubule segments also synthesize in large abundance tissue kallikrein (TK), a major kinin-forming enzyme. Tested was the hypothesis that TK and kinins are involved in controlling RTCa transport by studying TK (TK-/-) or kinin B2 receptor (B2-/-)-deficient mice on different Ca diets. On a 0.9% wt/wt Ca diet, 129Sv or C57Bl/6 TK-/- mice excreted significantly more Ca in urine than their wild-type (WT) littermates. There was no difference between TK-/- and WT mice for plasma concentrations of Ca, Mg, creatinine, parathyroid hormone, or 1,25-dihydroxyvitamin D. On a low Ca (LCa) diet (0.01% wt/wt), urinary Ca excretion decreased in both TK-/- and WT mice but still remained higher in TK-/- mice compared with WT. The plasma Ca concentration was unchanged in C57Bl/6 TK-/- mice but decreased significantly in 129Sv TK-/- mice. Taken together, these data demonstrate that TK deficiency led to impaired RTCa absorption. On the LCa diet, renal TK gene expression doubled in WT mice. No change in urinary Ca excretion was observed in B2-/- mice, even after treatment with a kinin B1-receptor antagonist, and these mice adapted normally to the LCa diet. TK deficiency had no effect on the renal abundance of distal Ca transporter mRNA. These data suggest that TK may be a physiologic regulator of RTCa transport, acting through a non-kinin-mediated mechanism.
Picard
Nicolas
N
INSERM, Unité 652, and Institut Fédératif de Recherche 58, Paris, France.
Van Abel
Monique
M
Campone
Christelle
C
Seiler
Michelle
M
Bloch-Faure
May
M
Hoenderop
Joost G J
JG
Loffing
Johannes
J
Meneton
Pierre
P
Bindels
René J M
RJ
Paillard
Michel
M
Alhenc-Gelas
François
F
Houillier
Pascal
P
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D020840:Tissue Kallikreins / Q000172:deficiency* / Q000235:genetics*
D012333:RNA, Messenger; D020840:Tissue Kallikreins; D002118:Calcium