Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells
| dc.contributor.author | Carraro-Lacroix, Luciene R. [UNIFESP] | |
| dc.contributor.author | Malnic, Gerhard | |
| dc.contributor.author | Girardi, Adriana C. C. | |
| dc.contributor.institution | Universidade de São Paulo (USP) | |
| dc.contributor.institution | Universidade Federal de São Paulo (UNIFESP) | |
| dc.date.accessioned | 2016-01-24T13:58:56Z | |
| dc.date.available | 2016-01-24T13:58:56Z | |
| dc.date.issued | 2009-12-01 | |
| dc.description.abstract | Carraro-Lacroix LR, Malnic G, Girardi AC. Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells. Am J Physiol Renal Physiol 297: F1647-F1655, 2009. First published September 23, 2009; doi:10.1152/ajprenal.00082.2009.-The gut incretin hormone glucagon-like peptide 1 (GLP-1) is released in response to ingested nutrients and enhances insulin secretion. in addition to its insulinotropic properties, GLP-1 has been shown to have natriuretic actions paralleled by a diminished proton secretion. We therefore studied the role of the GLP-1 receptor agonist exendin-4 in modulating the activity of Na+/H+ exchanger NHE3 in LLC-PK1 cells. We found that NHE3-mediated Na+-dependent intracellular pH (pH(i)) recovery decreased similar to 50% after 30-min treatment with 1 nM exendin-4. Pharmacological inhibitors and cAMP analogs that selectively activate protein kinase A (PKA) or the exchange protein directly activated by cAMP (EPAC) demonstrated that regulation of NHE3 activity by exendin-4 requires activation of both cAMP downstream effectors. This conclusion was based on the following observations: 1) the PKA antagonist H-89 completely prevented the effect of the PKA activator but only partially blocked the exendin-4-induced NHE3 inhibition; 2) the MEK1/2 inhibitor U-0126 abolished the effect of the EPAC activator but only diminished the exendin-4-induced NHE3 inhibition; 3) combination of H-89 and U-0126 fully prevented the effect of exendin-4 on NHE3; 4) no additive effect in the inhibition of NHE3 activity was observed when exendin-4, PKA, and EPAC activators were used together. Mechanistically, the inhibitory effect of exendin-4 on pHi recovery was associated with an increase of NHE3 phosphorylation. Conversely, this inhibition took place without changes in the surface expression of the transporter. We conclude that GLP-1 receptor agonists modulate sodium homeostasis in the kidney, most likely by affecting NHE3 activity. | en |
| dc.description.affiliation | Univ São Paulo, Sch Med, Inst Heart, Lab Genet & Mol Cardiol,InCor, BR-05403900 São Paulo, Brazil | |
| dc.description.affiliation | Univ São Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05403900 São Paulo, Brazil | |
| dc.description.affiliation | Universidade Federal de São Paulo, Dept Physiol, São Paulo, Brazil | |
| dc.description.affiliationUnifesp | Universidade Federal de São Paulo, Dept Physiol, São Paulo, Brazil | |
| dc.description.source | Web of Science | |
| dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) | |
| dc.description.sponsorship | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) | |
| dc.description.sponsorshipID | FAPESP: 07/52945-8 | |
| dc.description.sponsorshipID | FAPESP: 04/01683-5 | |
| dc.format.extent | F1647-F1655 | |
| dc.identifier | http://dx.doi.org/10.1152/ajprenal.00082.2009 | |
| dc.identifier.citation | American Journal of Physiology-renal Physiology. Bethesda: Amer Physiological Soc, v. 297, n. 6, p. F1647-F1655, 2009. | |
| dc.identifier.doi | 10.1152/ajprenal.00082.2009 | |
| dc.identifier.issn | 1931-857X | |
| dc.identifier.uri | http://repositorio.unifesp.br/handle/11600/31964 | |
| dc.identifier.wos | WOS:000273288100018 | |
| dc.language.iso | eng | |
| dc.publisher | Amer Physiological Soc | |
| dc.relation.ispartof | American Journal of Physiology-renal Physiology | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.subject | dipeptidyl peptidase IV | en |
| dc.subject | sodium reabsorption | en |
| dc.subject | intracellular pH | en |
| dc.subject | protein kinase A | en |
| dc.subject | exchange protein directly activated by cAMP | en |
| dc.title | Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells | en |
| dc.type | info:eu-repo/semantics/article |