title: Kinetics of erythrocyte plasma membrane (Ca2+, Mg2+)ATPase in familial benign hypercalcemia.
abstract: The pathogenesis of familial benign hypercalcemia (FBH) is unknown. Possible explanations for the disorder include a set-point error in parathyroid gland regulation and intrinsic renal hyperreabsorption of calcium. Thus, FBH may involve an alteration in cellular calcium transport, especially in renal and parathyroid cells. A primary mediator of cellular calcium transport is (Ca2+,Mg2+)ATPase. Therefore, we examined in detail the kinetics of (Ca2+,Mg2+)ATPase activity in erythrocyte plasma membranes from 11 patients with FBH from 7 families, 5 patients with untreated primary hyperparathyroidism, and equal numbers of age- and sex-matched normal subjects. (Ca2+,Mg2+)ATPase activity was measured in isolated membranes as a function of free calcium (0.05-300 mumol/L) in the presence or absence of calmodulin (600 nmol/L) and as a function of calmodulin (0-1800 nmol/L). We found no significant differences in calcium- or calmodulin-dependent (Ca2+,Mg2+)ATPase kinetics between patients with FBH or primary hyperparathyroidism and their age- and sex-matched normal subjects. None of the kinetic parameters was correlated with serum calcium or serum PTH values. We postulate that a mechanism other than a global defect in (Ca2+,Mg2+)ATPase activity is responsible for the hypercalcemia in patients with FBH.
authors.affiliation: Department of Medicine, Mayo Clinic and Foundation, Mayo Medical School, Rochester, Minnesota 55905.
authors.forename: H J
authors.initials: HJ
authors.lastname: Donahue
authors.forename: J T
authors.initials: JT
authors.lastname: Penniston
authors.forename: H
authors.initials: H
authors.lastname: Heath
mesh_terms: D000328:Adult; D001692:Biological Transport; D017301:Ca(2+) Mg(2+)-ATPase / Q000097:blood* / Q000235:genetics; D002118:Calcium / Q000097:blood / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000097:blood* / Q000235:genetics; D002147:Calmodulin / Q000097:blood / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000201:enzymology*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D006961:Hyperparathyroidism / Q000097:blood / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged
chemical_list: D002147:Calmodulin; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D002118:Calcium