Phosphonoformic acid blunts adaptive response of renal and intestinal Pi transport.
Parenteral administration of phosphonoformic acid (PFA) results in phosphaturia, but the effects of oral PFA on Pi handling are not known. To assess this effect, PFA was administered in drinking water for 5 days to rats stabilized on normal (NPD) or low (LPD) phosphorus diets. In renal brush-border membrane vesicles (BBMV), kinetic studies showed a higher apparent Vmax for Pi in rats on LPD compared with rats on NPD (1,840 +/- 274 vs. 1,111 +/- 192 pmol.mg-1.5 s-1, respectively, P < 0.05, n = 5). In LPD rats, PFA reduced the apparent Vmax for Pi to 1,047 +/- 191 pmol.mg-1.5 s-1 (P < 0.05, n = 5) with no change in the apparent Km. Similarly, there was a higher apparent Vmax for Pi in intestinal BBMV from rats on LPD compared with rats on NPD. In LPD rats, PFA reduced the apparent Vmax for Pi with no change in the apparent Km. Oral PFA had no effect on the kinetics of Pi transport in renal or intestinal BBMV from rats on NPD. Pi-protectable [14C]PFA binding was lower in renal BBMV from PFA-treated LPD rats, but membrane fluidity was not different. Orally administered PFA can blunt the adaptive response of the renal and intestinal BBM to an LPD. The downregulation of Na(+)-Pi cotransport is mediated through a reduction in the number of Na(+)-Pi cotransporters.
Loghman-Adham
M
M
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.
Levi
M
M
Scherer
S A
SA
Motock
G T
GT
Totzke
M T
MT
D000042:Absorption; D000222:Adaptation, Physiological / Q000187:drug effects*; D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D017245:Foscarnet / Q000378:metabolism / Q000494:pharmacology*; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016226:Phosphorus, Dietary / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D010710:Phosphates; D016226:Phosphorus, Dietary; D017245:Foscarnet