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Glucagon‐like peptide‐1 downregulates Na+/H+ exchanger NHE3 activity in rat renal proximal tubule
Author(s) -
Pacheco Bruna Piccolo Muniz,
Lessa Lucilia Maria Abreu,
Oricchio Felipe Theocharides,
Malnic Gerhard,
Girardi Adriana Castello Costa
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.606.33
Subject(s) - reabsorption , chemistry , sodium–hydrogen antiporter , medicine , endocrinology , bicarbonate , nephron , renal sodium reabsorption , convoluted tubule , sodium , tubular fluid , tubule , kidney , excretion , biochemistry , organic chemistry
The glucagon‐like peptide‐1 (GLP‐1) receptor has recently been detected in cultured renal proximal tubule cells, where GLP‐1 reduces sodium reabsorption. The present study was undertaken to evaluate the role of GLP‐1 in modulating the in vivo activity of NHE3 which represents the major route for proximal tubular (PT) sodium and bicarbonate reabsorption. Compared to controls, rats treated with 1.0 μg/kg×min GLP ( i.v. ) for the period of 1 hour exhibited increased urine output (54.3 ± 5.5 vs. 22.4 ± 2.5 mL/min×Kg; P=0.001), fractional sodium excretion (0.41 ± 0.12 vs. 0.14 ± 0.03%; P = 0.02) as well as lithium clearance, an index of end‐proximal tubule delivery (2.2 ± 0.4 vs. 1.3 ± 0.2 mL/min; P < 0.01). Real time RT‐PCR in microdissected rat nephron segments revealed GLP‐1 mRNA expression only in the proximal convoluted tubule. Experiments of stationary microperfusion performed in rat renal PT revealed that GLP‐1 significantly reduced bicarbonate reabsorption (1.16 ± 0.13 vs. 2.11 ± 0.17 nmol/cm 2 ×s; P = 0.002). Reduced PT bicarbonate flux rate was associated with a significant increase of NHE3 phosphorylation at the PKA consensus sites (serines 552 and 605) and decreased expression of the exchanger in microvillus membrane vesicles. We conclude that GLP‐1 has diuretic and natriuretic effects which are mediated at least partially by downregulation of PT NHE3 transport function.