| Full text | |
| Author(s): |
Girardi, Adriana Castello Costa
;
Fukuda, Lívia Emy
;
Rossoni, Luciana Venturini
;
Malnic, Gerhard
[4]
;
Rebouças, Nancy Amaral
Total Authors: 5
|
| Document type: | Journal article |
| Source: | American Journal of Physiology : Renal Physiology; v. 294, n. 2, p. F414-F422, Feb. 2008. |
| Field of knowledge: | Biological Sciences - Physiology |
| Abstract | |
In the microvillar microdomain of the kidney brush border, sodium hydrogen exchanger type 3 (NHE3) exists in physical complexes with the serine protease dipeptidyl peptidase IV (DPPIV). The purpose of this study was to explore the functional relationship between NHE3 and DPPIV in the intact proximal tubule in vivo. To this end, male Wistar rats were treated with an injection of the reversible DPPIV inhibitor Lys [Z(NO2)]-pyrrolidide (I40; 60 mg·kg-1·day-1 ip) for 7 days. Rats injected with equal amounts of the noninhibitory compound Lys[Z(NO2)]-OH served as controls. Na+-H+ exchange activity in isolated microvillar membrane vesicles was 45 ± 5% decreased in rats treated with I40. Membrane fractionation studies using isopycnic centrifugation revealed that I40 provoked redistribution of NHE3 along with a small fraction of DPPIV from the apical enriched microvillar membranes to the intermicrovillar microdomain of the brush border. I40 significantly increased urine output (67 ± 9%; P < 0.01), fractional sodium excretion (63 ± 7%; P < 0.01), as well as lithium clearance (81 ± 9%; P < 0.01), an index of end-proximal tubule delivery. Although not significant, a tendency toward decreased blood pressure and plasma pH/HCO3- was noted in I40-treated rats. These findings indicate that inhibition of DPPIV catalytic activity is associated with inhibition of NHE3-mediated NaHCO3 reabsorption in rat renal proximal tubule. Inhibition of apical Na+-H+ exchange is due to reduced abundance of NHE3 protein in the microvillar microdomain of the kidney brush border. Moreover, this study demonstrates a physiologically significant interaction between NHE3 and DPPIV in the intact proximal tubule in vivo. (AU) | |
| FAPESP's process: | 07/52945-8 - Importância do peptídeo semelhante ao glucagon 1 (GLP-1) na manutenção do volume extracelular: abordagem funcional, farmacológica e molecular |
| Grantee: | Adriana Castello Costa Girardi |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 02/13684-0 - Modificações na reatividade vascular a fenilefrina e na atividade e expressão de Na+K+ATPase em artérias de ratos normotensos e espontaneamente hipertensos submetidos ao tratamento crônico com ouabaína: modulação endotelial |
| Grantee: | Luciana Venturini Rossoni |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 04/01683-5 - Molecular and functional studies of membrane ion transporters |
| Grantee: | Gerhard Malnic |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 05/52102-5 - Caracterizacao funcional da interacao entre o trocador na+/h+ nhe3 e a enzima dipeptidil peptidase iv (dppiv) em tecido renal. |
| Grantee: | Adriana Castello Costa Girardi |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |