title: Glomerular tubular balance is suppressed in adenosine type 1 receptor-deficient mice.
abstract: Glomerular tubular balance maintains a stable fractional solute and fluid reabsorption in the proximal tubule over a range of glomerular filtration rates. The mediators of this process are unknown. We tested the hypothesis that adenosine, produced in proximal tubule cells acting on adenosine type 1 receptors (A(1)-AR) promotes Na(+) and fluid uptake and mediates glomerular tubular balance. Absolute proximal fluid reabsorption (J(v)) was measured by in vivo microperfusion in A(1)-AR knockout and wild-type mice during perfusion of the closed proximal tubule at 2-10 nl/min. J(v) increased with perfusate flow from 2-4 nl/min in both strains, but the fractional increase was lower in A(1)-AR(-/-) mice (A(1)-AR(+/+): 114% vs. A(1)-AR(-/-): 38%; P < 0.001), suggesting reduced glomerular tubular balance (GTB). At higher perfusion rates, J(v) increased modestly in both strains, indicating less GTB at higher flow. The physiological effects of reduced GTB in A(1)-AR(-/-) mice were assessed from the response to an acute volume load (1 ml/2 min). Na(+) excretion and urine flow increased 76 and 73% more in A(1)-AR(-/-) mice than A(1)-AR(+/+) over the following 30 min, accompanied by a higher proximal tubule flow (A(1)-AR(-/-): 6.9 ± 0.9 vs. A(1)-AR(+/+): 5.2 ± 0.6 nl/min; P < 0.05). The expression of the sodium-hydrogen exchanger 3 and sodium phosphate cotransporter-2 were similar between strains. In conclusion, GTB is dependent on adenosine acting on type 1 receptors in the proximal tubule. This may contribute to acute changes in Na(+) and fluid reabsorption.
authors.affiliation: Dept. of Medicine, Georgetown University, 4000 Reservoir Rd., Washington, DC 20057, USA.
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Bell
authors.forename: Zaiming
authors.initials: Z
authors.lastname: Luo
authors.forename: William J
authors.initials: WJ
authors.lastname: Welch
mesh_terms: D000241:Adenosine / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006439:Hemodynamics / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D066298:In Vitro Techniques; D007444:Inulin; D007678:Kidney Glomerulus / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009399:Nephrons / Q000502:physiology; D010477:Perfusion; D043682:Receptor, Adenosine A1 / Q000235:genetics* / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000378:metabolism; D014563:Urodynamics / Q000502:physiology
chemical_list: D043682:Receptor, Adenosine A1; C493558:Slc34a2 protein, mouse; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D007444:Inulin; D012964:Sodium; D000241:Adenosine
references.citation: J Card Fail. 2007 Oct;13(8):609-17
references.pmid: 17923351
references.citation: Hypertension. 2007 Oct;50(4):744-9
references.pmid: 17664389
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 May;290(5):R1324-9
references.pmid: 16357099
references.citation: Am J Physiol. 1978 Aug;235(2):F142-50
references.pmid: 686177
references.citation: Am J Physiol. 1975 Jan;228(1):98-106
references.pmid: 1147033
references.citation: J Am Coll Cardiol. 2007 Oct 16;50(16):1551-60
references.pmid: 17936154
references.citation: Kidney Int Suppl. 1982 Aug;12:S136-42
references.pmid: 6957669
references.citation: Annu Rev Physiol. 1987;49:251-73
references.pmid: 3551801
references.citation: Kidney Int. 1972 Jun;1(6):397-405
references.pmid: 4671208
references.citation: Am J Physiol. 1993 Oct;265(4 Pt 2):F504-10
references.pmid: 8238379
references.citation: Am J Physiol Renal Physiol. 2008 Jul;295(1):F37-41
references.pmid: 18480183
references.citation: Exp Physiol. 1996 Jan;81(1):95-105
references.pmid: 8869142
references.citation: J Clin Invest. 1966 Apr;45(4):590-602
references.pmid: 5937030
references.citation: Am J Physiol. 1990 Mar;258(3 Pt 2):F553-61
references.pmid: 1969237
references.citation: J Clin Invest. 1972 Jan;51(1):127-33
references.pmid: 5007043
references.citation: Kidney Int. 2004 Apr;65(4):1180-90
references.pmid: 15086457
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 Nov;281(5):R1362-7
references.pmid: 11641103
references.citation: J Clin Invest. 1986 Dec;78(6):1547-57
references.pmid: 3782470
references.citation: J Pharmacol Exp Ther. 1990 Feb;252(2):689-95
references.pmid: 2313594
references.citation: Br J Pharmacol. 1993 May;109(1):271-7
references.pmid: 8495243
references.citation: Circulation. 2002 Mar 19;105(11):1348-53
references.pmid: 11901047
references.citation: J Clin Invest. 1971 Jan;50(1):77-89
references.pmid: 5543884
references.citation: Kidney Int. 1991 May;39(5):836-42
references.pmid: 1648643
references.citation: Hypertension. 1995 Dec;26(6 Pt 2):1181-5
references.pmid: 7498992
references.citation: J Am Soc Nephrol. 1999 Apr;10(4):714-20
references.pmid: 10203354
references.citation: J Clin Invest. 1976 Nov;58(5):1110-8
references.pmid: 993334
references.citation: J Pharmacol Exp Ther. 2005 Apr;313(1):403-9
references.pmid: 15590766
references.citation: Acta Physiol (Oxf). 2007 May;190(1):87-96
references.pmid: 17428236
references.citation: Am J Physiol. 1967 Sep;213(3):809-18
references.pmid: 6036804
references.citation: J Am Soc Nephrol. 2003 Jul;14(7):1720-30
references.pmid: 12819231
references.citation: Nephrol Dial Transplant. 2004 May;19(5):1077-82
references.pmid: 14993484
references.citation: J Clin Invest. 1973 Apr;52(4):843-9
references.pmid: 4693649
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9983-8
references.pmid: 11504952
references.citation: J Am Coll Cardiol. 2000 Jan;35(1):56-9
references.pmid: 10636259
references.citation: J Clin Invest. 1968 Sep;47(9):2016-24
references.pmid: 4300070
references.citation: Pflugers Arch. 2004 May;448(2):214-21
references.pmid: 14767772
references.citation: Curr Opin Nephrol Hypertens. 2003 Sep;12(5):497-502
references.pmid: 12920396
references.citation: J Clin Invest. 1965 Aug;44:1410-6
references.pmid: 14322045
references.citation: J Pharmacol Exp Ther. 2006 Jun;317(3):1219-29
references.pmid: 16527902
references.citation: Am J Physiol. 1993 Oct;265(4 Pt 2):F511-9
references.pmid: 8238380
references.citation: Hypertension. 1996 Mar;27(3 Pt 1):404-7
references.pmid: 8698445
references.citation: Hypertension. 1990 May;15(5):451-8
references.pmid: 2185149
references.citation: Jpn J Pharmacol. 1995 Aug;68(4):389-96
references.pmid: 8531413