Different mechanisms of adaptive increase in Na+-Pi cotransport across renal brush-border membrane.
We explored the biochemical mechanism by which thyroid hormone (T3) and low-phosphate diet (LPD) cause an adaptive increase in Na+-Pi cotransport across renal brush-border membrane (BBM). The rate of Na+-Pi cotransport was determined by 32Pi uptake by BBM vesicles (BBMV), and the number of Na+-Pi symporters was assessed by binding of [14C]phosphonoformic acid (PFA) on BBMV. In BBMV of both T3-treated rats and LPD-fed rats, the Na+ gradient-dependent 32Pi uptake increased (Vmax increased; Km Pi was not changed). The Na+-dependent [14C]PFA binding on BBMV increased (higher Vmax, no change in Km PFA) in response to T3, but it remained unchanged in rats fed LPD. Both the increase of Na+-Pi cotransport and of Na+-dependent [14C]PFA binding in response to T3 were blocked by actinomycin D or cycloheximide. Addition of benzyl alcohol to BBMV in vitro increased Na+-Pi cotransport, but [14C]PFA binding did not change; the [3H]phlorizin binding and cotransports of other solutes decreased or did not change. The exposure of BBMV to cholesterol decreased Na+-Pi cotransport without changing [14C]PFA binding. We suggest that the adaptive increase of Na+-Pi cotransport elicited by T3 is due to an increase in number of Na+-Pi cotransporters in BBM. In contrast, in response to LPD the number of Na+-Pi cotransporters is unchanged, and the increased Na+-Pi cotransport is due to faster translocation of Na+ with Pi due to enhanced fluidity of BBM.
Yusufi
A N
AN
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
Szczepanska-Konkel
M
M
Hoppe
A
A
Dousa
T P
TP
D000222:Adaptation, Physiological; D000818:Animals; D001696:Biomechanical Phenomena; D002352:Carrier Proteins / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004032:Diet; D017245:Foscarnet; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008871:Microvilli / Q000378:metabolism; D010695:Phlorhizin / Q000378:metabolism; D010710:Phosphates / Q000008:administration & dosage / Q000494:pharmacology; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014284:Triiodothyronine / Q000494:pharmacology
D002352:Carrier Proteins; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014284:Triiodothyronine; D003609:Dactinomycin; D010758:Phosphorus; D017245:Foscarnet; D003513:Cycloheximide; D010695:Phlorhizin; D010746:Phosphonoacetic Acid