title: Tubuloglomerular feedback and renal function in mice with targeted deletion of the type 1 equilibrative nucleoside transporter.
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.
authors.affiliation: Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lingli
authors.initials: L
authors.lastname: Li
authors.forename: Diane
authors.initials: D
authors.lastname: Mizel
authors.forename: Yuning
authors.initials: Y
authors.lastname: Huang
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisner
authors.forename: Marion
authors.initials: M
authors.lastname: Hoerl
authors.forename: Manfred
authors.initials: M
authors.lastname: Thiel
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schnermann
mesh_terms: D000241:Adenosine / Q000097:blood; D000243:Adenosine Deaminase / Q000096:biosynthesis; D000818:Animals; D062186:Arterial Pressure / Q000235:genetics; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics / Q000502:physiology*; D033722:Equilibrative-Nucleoside Transporter 2 / Q000096:biosynthesis; D005260:Female; D017353:Gene Deletion; D005919:Glomerular Filtration Rate / Q000235:genetics; D006339:Heart Rate / Q000235:genetics; D007288:Inosine / Q000097:blood; D007678:Kidney Glomerulus / Q000502:physiology; D007684:Kidney Tubules / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis; D012083:Renin / Q000097:blood
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D018047:Receptors, Purinergic P1; C498476:SLC29A1 protein, mouse; C486681:Slc29a2 protein, mouse; D007288:Inosine; D012083:Renin; D000243:Adenosine Deaminase; D000241:Adenosine