Loghman-Adham M, Levi M, Scherer S A, Motock G T, Totzke M T
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.
Am J Physiol. 1993 Dec;265(6 Pt 2):F756-63. doi: 10.1152/ajprenal.1993.265.6.F756.
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.
经肠胃外途径给予膦甲酸（PFA）会导致磷酸盐尿，但口服PFA对磷（Pi）处理的影响尚不清楚。为评估这种影响，将PFA添加到饮用水中，连续5天给予维持正常（NPD）或低磷（LPD）饮食的大鼠。在肾刷状缘膜囊泡（BBMV）中进行的动力学研究表明，与NPD饮食的大鼠相比，LPD饮食的大鼠Pi的表观最大反应速度（Vmax）更高（分别为1,840±274与1,111±192 pmol·mg-1.5·s-1，P<0.05，n = 5）。在LPD饮食的大鼠中，PFA将Pi的表观Vmax降低至1,047±191 pmol·mg-1.5·s-1（P<0.05，n = 5），而表观米氏常数（Km）没有变化。同样，与NPD饮食的大鼠相比，LPD饮食的大鼠肠BBMV中Pi的表观Vmax更高。在LPD饮食的大鼠中，PFA降低了Pi的表观Vmax，而表观Km没有变化。口服PFA对NPD饮食大鼠肾或肠BBMV中Pi转运的动力学没有影响。在PFA处理的LPD饮食大鼠的肾BBMV中，Pi可保护的[14C]PFA结合较低，但膜流动性没有差异。口服PFA可减弱肾和肠BB对LPD的适应性反应。Na(+)-Pi共转运体的下调是通过减少Na(+)-Pi共转运体的数量来介导的。
