Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0221002 (primary hyperparathyroidism)
 4,921 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Kinetics of erythrocyte plasma membrane (Ca2+, Mg2+)ATPase in familial benign hypercalcemia. 252 97

It has been suggested that the parathyroid glands and the kidneys are insensitive to the high extracellular calcium levels found in familial benign hypercalcaemia (FBH) (familial hypocalciuric hypercalcaemia) and that there may be a general disorder of the plasma membrane 'calcium pump'. We have found that the activity of the calcium-stimulated, magnesium-dependent ATPase of erythrocyte ghost membranes from patients with FBH was significantly higher (p less than 0.01) than that from normal subjects. Values in FBH, as a group, were higher than those in primary hyperparathyroidism, but the difference was not significant. We suggest that the membrane abnormality in FBH could be a disorder of the regulation of the calcium pump.
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PMID:Calcium-ATPase activity in erythrocyte ghosts from patients with familial benign hypercalcaemia. 316 Jan 2

The chronic effect of PTH on erythrocyte membrane Ca transport was examined. (Ca+Mg)ATPase activity and passive Sr influx were measured to assess the rate of passive Ca influx (total and inhibited by dihydropyridines [DHPs]), in erythrocytes from patients with primary hyperparathyroidism and normal controls. Erythrocyte Sr influx was lower in patients, due to a decreased DHP-sensitive Sr influx. Conversely, efflux activity of (Ca+Mg)ATPase was not different in patients and controls. We hypothesize that in primary hyperparathyroidism chronic PTH stimulation may induce a downregulation of the erythrocyte Ca influx mediated by DHP-sensitive Ca carrier.
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PMID:Erythrocyte membrane calcium transport in patients with primary hyperparathyroidism. 806 Mar 33

The acute inhibitory effects of parathyroid hormone (PTH) on proximal tubule Na(+)-K(+)-ATPase (Na-K) and sodium-dependent phosphate (NaPi) transport have been extensively studied, while little is known about the chronic effects of PTH. Patients with primary hyperparathyroidism, a condition characterized by chronic elevations in PTH, exhibit persistent hypophosphatemia but not significant evidence of salt wasting. We postulate that chronic PTH stimulation results in differential desensitization of PTH responses. To address this hypothesis, we compared the effects of chronic PTH stimulation on Na-P(i) cotransporter (Npt2a) expression and Na-K activity and expression in Sprague Dawley rats, transgenic mice featuring parathyroid-specific cyclin D1 overexpression (PTH-D1), and proximal tubule cell culture models. We demonstrated a progressive decrease in brush-border membrane (BBM) expression of Npt2a from rats treated with PTH for 6 h or 4 days, while Na-K expression and activity in the basolateral membranes (BLM) exhibited an initial decrease followed by recovery to control levels by 4 days. Npt2a protein expression in PTH-D1 mice was decreased relative to control animals, whereas levels of Na-K, NHERF-1, and PTH receptor remained unchanged. In PTH-D1 mice, NpT2a mRNA expression was reduced by 50% relative to control mice. In opossum kidney proximal tubule cells, PTH decreased Npt2a mRNA levels. Both actinomycin D and cycloheximide treatment prevented the PTH-mediated decrease in Npt2a mRNA, suggesting that the PTH response requires transcription and translation. These findings suggest that responses to chronic PTH exposure are selectively regulated at a posttranscriptional level. The persistence of the phosphaturic response to PTH occurs through posttranscriptional mechanisms.
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PMID:Parathyroid hormone (PTH) decreases sodium-phosphate cotransporter type IIa (NpT2a) mRNA stability. 2334 72