Parathyroid hormone-induced translocation of Na-H antiporters in rat proximal tubules.
Parathyroid hormone (PTH) is believed to inhibit bicarbonate reabsorption by inhibiting Na-H antiport activity in proximal tubular brush-border membranes. The sequence of events triggered by PTH was investigated in a crude preparation of proximal tubules obtained by mechanical disruption and filtration through nylon mesh filters. Tubule samples were subjected to analytical subcellular fractionation after 2-, 5-, and 30-min treatments with 1 IU/ml PTH. These PTH-treatment intervals caused 54, 63, and 68% decreases in the Na-H antiport activity of a population of brush-border membrane vesicles that was resolved from a PTH-unresponsive brush-border population by density-gradient centrifugation. The rapid loss of Na-H antiport activity from the responsive population was accompanied by a transient increase in the Na-H antiport activity of a region of the density gradient, designated density window III, which was shown to contain two distinct membrane populations; these populations were both enriched in acid phosphatase activity, and one of them was also an important locus of galactosyltransferase activity. The increase in the Na-H antiport activity of window III accounted for 52% of the activity lost from the PTH-responsive population after 2 min, and for 43% of the activity lost after 5 min, but it was completely abolished after 25 more minutes in the presence of PTH. These observations suggest that PTH triggers a rapid translocation of Na-H antiporters from the microvillus membrane to a distinct membrane domain, where they are subsequently inactivated.
Hensley
C B
CB
Department of Physiology, University of Southern California School of Medicine, Los Angeles 90033.
Bradley
M E
ME
Mircheff
A K
AK
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002458:Cell Fractionation; D002499:Centrifugation, Density Gradient; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008962:Models, Theoretical; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D019379:Teriparatide
D002352:Carrier Proteins; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D017923:Sodium-Hydrogen Exchangers; D019379:Teriparatide; D000469:Alkaline Phosphatase; D000254:Sodium-Potassium-Exchanging ATPase