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Renal Caffeine Effects are Independent of NHE3 Abundance, Trafficking or Phosphorylation
Author(s) -
Rieg Timo,
Soleimani Manoocher,
Dominguez Rieg Jessica,
Busslinger Meinrad,
Fenton Robert
Publication year - 2015
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.29.1_supplement.970.4
Subject(s) - caffeine , chemistry , dids , endocrinology , medicine , reabsorption , pharmacology , sodium , biochemistry , membrane , organic chemistry
We have previously shown that the diuretic and natriuretic effect of caffeine is mediated by blockade of adenosine A 1 receptors and both effects are unaffected in the absence of renal tubular NHE3. However, compensatory mechanisms in tubulus‐specific NHE3 knockout mice may mask caffeine effects on NHE3 abundance, trafficking or phosphorylation. Wild‐type mice were randomized to acute application of caffeine (45 mg/kg, n =6) or water (vehicle, n =6) via oral gavage (1% of bw) and kidneys harvested after 60 min. Renal NHE3 protein abundance (vehicle: 100±8, caffeine: 101±13 %), phosphorylation at serine 552 (vehicle: 100±14, caffeine: 86±10 %) or serine 605 (vehicle: 100±8, caffeine: 96±9 %) were comparable between groups. Membrane abundance analyzed via semi‐quantitative confocal laser scanning microscopy showed no significant difference between groups. We hypothesized that the Na + /HCO 3 ‐ cotransporter NBC1 (NBCe1) may be responsible for mediating the caffeine effects. Mice were treated with vehicle (0.85% NaCl, n =12) or DIDS (NBC inhibitor, 40 mg/kg i.p., 2 µl/g bw, n =10) 30 min before application of caffeine (45 mg/kg, 3% of bw by oral gavage), and a 3 hour urine collection performed. DIDS+caffeine resulted in a significantly lower urinary flow rate vs vehicle+caffeine (191±31 vs 296±16 nl/min/g, P <0.05) which was not different from vehicle alone (203±19 nl/min/g, n =12). Our data show that NHE3 is not required for caffeine‐induced renal effects but point towards a role of NBC1 in mediating caffeine‐induced diuresis.