Localization of tubular uptake segment of filtered Cystatin C and Aprotinin in the rat kidney.
OBJECTIVE
The renal tubular uptake of 125I-Aprotinin (*Ap) is on average located more superficially than its filtration site, causing transfer of some of *Ap filtered in deep to more superficial cortical zones. 125I-Cystatin C (*Cy) showed less uptake in deep cortical zones than Ap, suggesting a longer and/or a more superficial tubular uptake site. To test that hypothesis and to quantify the outward transfer of the filtered polypeptides, we estimated the tubular uptake pattern of the tracers in perfusion fixed rat kidneys after intravenous injection of *Cy and *Ap.


METHODS
Autoradiographs were made from 10 mum thick slices of Microfil nephron casts from outer (OC), middle (MC) and inner (IC) cortical zones to quantify cortical border-crossing *Ap transfer. Single nephron glomerular filtration rate (snGFR) was estimated as the zonal uptake of *Ap corrected for *Ap transfer, divided by its time-integrated plasma concentration and the zonal number of glomeruli.


RESULTS
*Ap and *Cy uptake fell exponentially along the proximal convoluted tubule (PCT), indicating an uptake proportional to luminal concentration. Uptake in IC exceeded that in MC and OC nephrons. The per cent PCT length with *Cy uptake (67.2 +/- 1.6) exceeded that of *Ap (54.6 +/- 1.8). The zonal border-crossing PCT length (29-34% of total PCT) from deep to more superficial cortical zones transferred 4-6% more *Cy than *Ap.


CONCLUSIONS
Greater tubular uptake length of *Cy than of *Ap causes more cortical border-crossing of *Cy. The zonal snGFR estimated from Aprotinin uptake corrected for border-crossing agreed well with that obtained with the Hanssen ferrocyanide technique.
Department of Physiology, University of Bergen, Bergen, Norway. dadash.baran@biomed.uib.no
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Baran
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Tenstad
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Aukland
D000818:Animals; D007611:Aprotinin / Q000493:pharmacokinetics*; D055316:Cystatin C; D015891:Cystatins / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007668:Kidney / Q000033:anatomy & histology; D007678:Kidney Glomerulus / Q000033:anatomy & histology; D007687:Kidney Tubules, Proximal / Q000033:anatomy & histology / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley
C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D007457:Iodine Radioisotopes; D007611:Aprotinin