Phosphate transport in brush border membranes from uremic rats. Response to phosphonoformic acid.
Phosphate retention in chronic renal failure may result in the development of secondary hyperparathyroidism and renal osteodystrophy. Thus, the addition of a specific phosphaturic agent may be beneficial in the treatment of chronic renal failure. Phosphonoformic acid (PFA), a specific and competitive inhibitor of Na(+)-Pi cotransport in renal and intestinal brush border membrane vesicles (BBMV), can induce phosphaturia in thyroparathyroidectomized (TPTX) rats. The aim of this study was to determine if PFA retains its inhibitory activity in uremic intestine and kidney. The effect of PFA, and its derivative phosphonoacetic acid (PAA), added in vitro, on Pi transport in BBMV prepared from the intestine and the remnant kidney of 5/6 nephrectomized (NX) rats was studied. In intestinal BBMV, the time course of Pi transport was not significantly different between NX and sham-operated (SH) control rats. Compared with SH, Na(+)-dependent Pi transport was reduced in BBMV from remnant kidney of NX, with no difference in Na(+)-independent or equilibrium uptakes. The reduced transport was specific for Pi with no change in Na+ gradient-dependent L-proline uptake, suggesting a normal Na+ conductance in uremic BBM. PFA and PAA produced a marked inhibition of Na(+)-Pi cotransport in intestinal and renal BBMV from NX and SH with similar relative inhibitory potency in uremic and control BBMV. It was concluded that the relative inhibitory potency of PFA or PAA on intestinal and renal Na(+)-Pi cotransport is preserved in uremia.
Loghman-Adham
M
M
Department of Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, MN.
Szczepanska-Konkel
M
M
Dousa
T P
TP
D000818:Animals; D017245:Foscarnet / Q000494:pharmacology*; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000378:metabolism*
D010710:Phosphates; D017245:Foscarnet; D010746:Phosphonoacetic Acid