Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study shows that carbon tetrachloride fails to cause hypercalcemia in the serum and liver of rats after parathyroidectomy. Secondly, a diminution in the activity of calcium-dependent proteolytic enzyme, phospholipase A2 occurs in parathyroidectomized rats, suggesting a plausible protective mechanism against carbon tetrachloride toxicity.
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PMID:Effect of parathyroidectomy on calcium and phospholipase A2 in the liver of carbon tetrachloride-treated rats. 177 38

PGE2 overproduction by a nephroblastoma associated with hypercalcemia was clearly demonstrated in a 2-month-old girl. Compared with normal tissue, tumor showed greater phospholipase A2 and PGE2 synthetase activities but metabolized PGE2 at a faster rate. Of the enzymes involved in PGE2 synthesis, those which transform arachidonic acid into PGE2 seem to be more active.
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PMID:Synthesis and catabolism of PGE2 by a nephroblastoma associated with hypercalcemia without bone metastases. 633 25

The extracellular Ca(2+)-sensing receptor (CaR) responds to polycations, including Ca(2+) and neomycin. This receptor is a physiological regulator of systemic Ca(2+) metabolism and may also mediate the toxic effects of hypercalcemia. A number of divalent cations, including Pb(2+), Co(2+), Cd(2+), and Fe(2+), are toxic to the kidney, brain, and other tissues where the CaR is expressed. To determine which divalent cations can activate the CaR, we expressed the human CaR in HEK-293 cells and measured activation of phospholipase A(2) (PLA(2)) and the mitogen-activated protein kinase p42ERK in response to potential agonists for the receptor. HEK-293 cells expressing the nonfunctional mutant CaR R796W served as controls. Extracellular Ca(2+), Ba(2+), Cd(2+), Co(2+), Fe(2+), Gd(3+), Ni(2+), Pb(2+), and neomycin activated the CaR, but Hg(2+) and Fe(3+) did not. We analyzed the kinetics of activation of p42ERK and PLA(2) by the CaR in response to Ca(2+), Co(2+), and Pb(2+). The EC(50) values ranged from approximately 0.1 mM for Pb(2+) to approximately 4.0 mM for Ca(2+). The Hill coefficients were >3, indicating multiple cooperative ligand binding sites or subunits. Submaximal concentrations of Ca(2+) and Pb(2+) were additive for activation of the CaR. The EC(50) for Ca(2+) or Pb(2+) was reduced four- to fivefold by the presence of the other ion. These divalent cations also activated PLA(2) via the CaR in Madin-Darby canine kidney cells that stably express the CaR. We conclude that many divalent cations activate the CaR and that their effects are additive. The facts that the CaR is a promiscuous polycation sensor and that the effects of these ions are additive to activate it suggest that the CaR may contribute to the toxicity of some heavy metals such as Pb(2+), Cd(2+), Co(2+), and Fe(2+) for the kidney and other tissues where it is expressed.
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PMID:Extracellular Ca(2+)-sensing receptor is a promiscuous divalent cation sensor that responds to lead. 1109 27