title: Further characterization of adenosine transport in renal brush-border membranes.
abstract: Adenosine transport has been further characterized in rat renal brush-border membranes (BBM). The uptake shows two components, one sodium-independent and one sodium-dependent. Both components reflect, at least partly, translocation via a carrier mechanism, since the presence of adenosine inside the vesicles stimulates adenosine uptake in the presence as well as in the absence of sodium outside the vesicles. The sodium-dependent component is saturable (Km adenosine = 2.9 microM, Vmax = 142 pmol/min per mg protein) and is abolished at low temperatures. The sodium-independent uptake has apparently two components: one saturable (Km = 4-10 microM, Vmax = 174 pmol/min per mg protein) and one non-saturable (Vmax = 3.4 pmol/min per mg protein, Km greater than 2000 microM). Inosine, guanosine, 2-chloroadenosine and 2'-deoxyadenosine inhibit the sodium-dependent and -independent transport, as shown by trans-stimulation experiments, probably because of translocation via the respective transporter. Uridine and dipyridamole inhibited only the sodium-dependent uptake. Other analogs of adenosine showed no inhibition. The kinetic parameters of the inhibitors of the sodium-dependent component were further investigated. Inosine was the most potent inhibitor with a Ki (1.9 microM) less than the Km of adenosine. This suggests a physiological role for the BBM ecto-adenosine deaminase (enzyme which extracellularly converts adenosine to inosine), balancing the amount of nucleoside taken up as adenosine or inosine by the renal proximal tubule cell.
authors.affiliation: Max-Planck-Institut für Systemphysiologie, Dortmund, F.R.G.
authors.forename: R
authors.initials: R
authors.lastname: Franco
authors.forename: J J
authors.initials: JJ
authors.lastname: Centelles
authors.forename: R K
authors.initials: RK
authors.lastname: Kinne
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism*; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D001692:Biological Transport; D002110:Caffeine / Q000494:pharmacology; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: D058892:Adenosine Deaminase Inhibitors; D007042:Hypoxanthines; D019271:Hypoxanthine; D002110:Caffeine; D012964:Sodium; D000241:Adenosine