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Target Concepts:
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Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The parathyroid cell detects changes in the extracellular ionized calcium concentration (Ca2 + o) with exquisite sensitivity, but the mechanisms through which it senses Ca2 + o have remained obscure. Recently, we isolated a cDNA encoding a Ca2 + o-sensing receptor from bovine parathyroid using expression cloning in Xenopus laevis oocytes. The expressed receptor stimulates
phospholipase C
and has a pharmacological profile almost identical to that of the native receptor. Furthermore, its deduced amino acid sequence confirms that it belongs to the superfamily of G-protein-coupled receptors. Receptor transcripts are present in parathyroid and other tissues sensing Ca2 + o (e.g., kidney and thyroidal C-cells) as well as those not known to be involved in Ca2+ homeostasis (viz., in the brain). We have also shown that mutations in the receptor cause three inherited disorders of calcium metabolism:
Familial hypocalciuric hypercalcemia
(
FHH
) and neonatal severe hyperparathyroidism (NSHPT) result from inactivating mutations, when present in the heterozygous and homozygous states, respectively, whereas an autosomal dominant form of hypocalcemia is due to an activating mutation. Thus this Ca2 + o-sensing receptor permits Ca2+o to act as an extracellular, first messenger in addition to its better known role as an intracellular second messenger.
...
PMID:The cloning of extracellular Ca(2+)-sensing receptors from parathyroid and kidney: molecular mechanisms of extracellular Ca(2+)-sensing. 760 78
Parathyroid cells recognize and respond to (i.e., "sense") minute perturbations in the extracellular ionized calcium concentration (Ca2+o), but the mechanisms underlying this process have remained obscure. Recently, we employed expression cloning in Xenopus laevis oocytes to isolate a cDNA coding for a Ca2+o-sensing receptor from bovine parathyroid. Like the native receptor, the cloned Ca2+o-sensing receptor stimulates
phospholipase C
(
PLC
) in a G-protein-dependent manner with a nearly identical pharmacological profile. Its deduced amino acid sequence confirms that it is a member of the superfamily of G-protein-coupled receptors (GPR). Transcripts for the receptor are expressed in parathyroid and other tissues that sense Ca2+o (viz., kidney and thyroidal C-cells) as well as those that have no known role in extracellular Ca2+ homeostasis, such as the brain. The availability of the cDNA clone for the Ca2+o-sensing receptor made it possible to test the hypothesis that mutations in the gene encoding the human homolog of the receptor cause inherited disorders of mineral ion metabolism.
Familial hypocalciuric hypercalcemia
(
FHH
) and neonatal severe hyperparathyroidism (NSHPT) are, in fact, caused by mutations that reduce the activity of the receptor when they are present in the heterozygous and homozygous states, respectively. In contrast, we have subsequently discovered a family in which a form of autosomal dominant hypocalcemia results from an activating mutation in the receptor gene. The Ca2+-sensing receptor, therefore, permits Ca2+o to play a "hormonelike" role as an extracellular first messenger in addition to its well described role as an important intracellular second messenger.
...
PMID:Cloning and functional characterization of extracellular Ca(2+)-sensing receptors from parathyroid and kidney. 857 1
