Ecto-5'-nucleotidase (cd73)-dependent and -independent generation of adenosine participates in the mediation of tubuloglomerular feedback in vivo

American Journal of Physiology. Renal Physiology
Dan Yang HuangHartmut Osswald

Abstract

Tubuloglomerular feedback (TGF) describes a sequence of events linking salt concentrations in tubular fluid at the macula densa to the vascular tone of the afferent arteriole and thus to the glomerular filtration rate (GFR) of the same nephron. The signal transduction pathways of TGF remain incompletely understood, but both ATP release from macula densa cells and local formation of adenosine were suggested to be involved in the process. To test the role of extracellular formation of adenosine by ecto-5'-nucleotidase (cd73) in TGF, in regulation of GFR, and in tubular reabsorption, renal clearance and micropunture experiments were performed in cd73 wild-type (cd73(+/+)) and knockout mice (cd73(-/-)). The cd73(-/-) mice presented normal mean arterial blood pressure, but modestly lower whole kidney and single nephron GFR (SNGFR). Fractional reabsorption of Na(+) and K(+) up to the late proximal tubule, distal tubule, as well as urine were not significantly different between cd73(-/-) and cd73(+/+) mice. Lack of cd73 resulted in a diminished TGF response, as indicated by smaller changes of stop-flow pressure in response to increasing loop of Henle perfusion from 0 to 25 nl/min, smaller differences in SNGFR determined from paired pr...Continue Reading

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