| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T01908 | ||||
| Target Name | Tissue kallikrein | ||||
| Target Type | Discontinued |
||||
| Action against Disease Model | Dermolastin | N-glycosylation and biological activity of recombinant h uMan alpha1-antitrypsin expressed in a novel h uMan neuronal cell line. | [553098] | Drug Info | |
| The Effect of Target Knockout, Knockdown or Genetic Variations | We showed in wild-type mice that renal K+ and tissue kallikrein(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 | [553098] | |||
| References | |||||
| Ref 553098 | N-glycosylation and biological activity of recombinant human alpha1-antitrypsin expressed in a novel human neuronal cell line. Biotechnol Bioeng. 2011 Sep;108(9):2118-28. doi: 10.1002/bit.23158. Epub 2011 Apr 20. | ||||
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