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Tubuloglomerular feedback and renal function in mice with targeted deletion of the type 1 equilibrative nucleoside transporter.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2013 Feb 15; Vol. 304 (4), pp. F382-9. Date of Electronic Publication: 2012 Dec 26. - Publication Year :
- 2013
-
Abstract
- A(1) adenosine receptors (A1AR) are required for the modulation of afferent arteriolar tone by changes in luminal NaCl concentration implying that extracellular adenosine concentrations need to change in synchrony with NaCl. The present experiments were performed in mice with a null mutation in the gene for the major equilibrative nucleoside transporter ENT1 to test whether interference with adenosine disposition by cellular uptake of adenosine may modify TGF characteristics. Responses of stop flow pressure (P(SF)) to maximum flow stimulation were measured in mice with either C57Bl/6 or SWR/J genetic backgrounds. Maximum flow stimulation reduced P(SF) in ENT1(-/-) compared with wild-type (WT) mice by 1.6 ± 0.4 mmHg (n = 28) and 5.8 ± 1.1 mmHg (n = 17; P < 0.001) in C57Bl/6 and by 1.4 ± 0.4 mmHg (n = 15) and 9 ± 1.5 mmHg (n = 9; P < 0.001) in SWR/J. Plasma concentrations of adenosine and inosine were markedly higher in ENT1(-/-) than WT mice (ado: 1,179 ± 78 and 225 ± 48 pmol/ml; ino: 179 ± 24 and 47.5 ± 9 pmol/ml). Renal mRNA expressions of the four adenosine receptors, ENT2, and adenosine deaminase were not significantly different between WT and ENT1(-/-) mice. No significant differences of glomerular filtration rate or mean arterial blood pressure were found while plasma renin concentration, and heart rates were significantly lower in ENT1(-/-) animals. In conclusion, TGF responsiveness is significantly attenuated in the absence of ENT1, pointing to a role of nucleoside transport in the NaCl-synchronous changes of extracellular adenosine levels in the juxtaglomerular apparatus interstitium.
- Subjects :
- Adenosine blood
Adenosine Deaminase biosynthesis
Animals
Arterial Pressure genetics
Equilibrative Nucleoside Transporter 1 genetics
Equilibrative-Nucleoside Transporter 2 biosynthesis
Female
Glomerular Filtration Rate genetics
Heart Rate genetics
Inosine blood
Kidney Glomerulus physiology
Male
Mice
Mice, Inbred C57BL
Receptors, Purinergic P1 biosynthesis
Renin blood
Equilibrative Nucleoside Transporter 1 physiology
Gene Deletion
Kidney Tubules physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 304
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 23269643
- Full Text :
- https://doi.org/10.1152/ajprenal.00581.2012