title: Reversal of decreased phosphorylation of sarcoplasmic reticulum calcium transport ATPase by 1,25-dihydroxycholecalciferol in experimental uremia.
abstract: When compared to that from sham-operated controls, sarcoplasmic reticulum isolated from skeletal muscle of uremic rabbits had a lower rate of calcium uptake and storing capacity. In vivo administration of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] restored the values in uremic animals toward normal. To obtain information about the mechanisms responsible for these differences, phosphorylation of the calcium transport ATPase was studied. The steady-state levels of phosphoprotein in uremic membranes were lower and returned to normal when the secosteroid was administered. Electrophoresis of the membranes phosphorylated with 32P-inosine triphosphate (32P-ITP) showed that the differences were related to a 100,000 dalton protein. The rate of phosphoprotein formation, determined with 32P-ITP and at 0 degrees C, was considerably lower in uremic than in control animals. Pretreatment with 1,25(OH)2D3 prevented this change. The hypothesis is advanced that the vitamin D metabolite affects the steady-state concentration and rate constant of formation of active sites in the Ca-ATPase. These results may partly explain the altered Ca transport function of the sarcoplasmic reticulum in experimental uremia.
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D008297:Male; D010750:Phosphoproteins / Q000096:biosynthesis; D010766:Phosphorylation; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D014511:Uremia / Q000201:enzymology / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D000252:Calcium-Transporting ATPases; D002117:Calcitriol; D002118:Calcium