title: Functional consequences at the single-nephron level of the lack of adenosine A1 receptors and tubuloglomerular feedback in mice.
abstract: Mice deficient for adenosine A1 receptors (A1AR) lack tubuloglomerular feedback (TGF). In vivo micropuncture experiments were performed under anesthesia in A1AR-deficient and wild-type littermate mice to study the effects of chronic absence of A1AR on fluid and Na(+) reabsorption along the nephron, as well as the functional consequences at the single-nephron level of the lack TGF. Evidence is provided for an A1AR-mediated tonic inhibition of Na(+) reabsorption in a water-impermeable segment of the loop of Henle, possibly the thick ascending limb. In contrast, proximal tubular reabsorption of fluid, Na(+) and K(+) was unaffected by the chronic absence of A1AR. Experiments in which artificial tubular fluid was added to free-flowing late-proximal tubules demonstrated an essential role of A1AR/TGF in the stabilization of fluid and Na(+) delivery to the distal nephron. Further, the occurrence of spontaneous oscillations of hydrostatic pressure in proximal tubule ( P(PT)) at a frequency of about 32 mHz depended on intact A1AR/TGF. In comparison, the normal, stabilizing reduction in P(PT) following the initial rise in P(PT) during sustained small increases in proximal tubular flow rate does not require A1AR/TGF; TGF-independent mechanisms appear to compensate in this regard for a lack of TGF under physiological conditions and the lack of TGF is unmasked only when supraphysiological flow rates overwhelm TGF-independent compensation.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Tübingen, Wilhelmstrasse 56, 72074, Tübingen, Germany. vvallon@ucsd.edu
authors.forename: V
authors.initials: V
authors.lastname: Vallon
authors.forename: K
authors.initials: K
authors.lastname: Richter
authors.forename: D Y
authors.initials: DY
authors.lastname: Huang
authors.forename: T
authors.initials: T
authors.lastname: Rieg
authors.forename: J
authors.initials: J
authors.lastname: Schnermann
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005246:Feedback; D005838:Genotype; D005919:Glomerular Filtration Rate; D006874:Hydrostatic Pressure; D007678:Kidney Glomerulus / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D008138:Loop of Henle / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009399:Nephrons / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000235:genetics* / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
chemical_list: D002712:Chlorides; D043682:Receptor, Adenosine A1; D012964:Sodium; D011188:Potassium