Molecular mechanisms underlying the sensing of extracellular Ca2+ by parathyroid and kidney cells.
Mineral ion homeostasis in mammalian species is maintained by a complex mechanism comprising sensors of the extracellular calcium concentration (Ca2+0) (i.e. parathyroid cells) as well as effectors that modify their translocation of mineral ions into and out of the extracellular fluid (e.g. kidney) in response to calciotropic hormones. Indirect evidence accumulated over the past decade suggested that parathyroid cells sense Ca2+0 through a cell surface receptor coupled to intracellular second messenger systems via one or more guanine nucleotide regulatory (G) proteins. More recently, Brown et al. employed expression cloning in Xenopus laevis oocytes to isolate a cDNA encoding a Ca2+0-sensing receptor from bovine parathyroid. The expressed receptor activates phospholipase C in a G-protein dependent manner and shows pharmacological properties almost identical to those of the native parathyroid receptor. Agonists for the receptor include not only divalent cations (e.g. Ca2+ and Mg2+) but also trivalent cations and even organic polycations such as neomycin. The deduced amino acid sequence of the cloned receptor confirms that it is a member of the superfamily of G-protein-coupled receptors. Receptor transcripts are present in parathyroid as well as in kidney, thyroid and brain. Therefore, this receptor may mediate the sensing of Ca2+0 not only by parathyroid cells but also by other tissues directly regulated by Ca2+0 (e.g. the thyroidal C cells and certain kidney cells) as well as those not currently known to be involved in calcium homeostasis (viz. in the brain).(ABSTRACT TRUNCATED AT 250 WORDS)
Brown
E M
EM
Endocrine-Hypertension Division, Brigham and Women's Hospital, Boston, MA, USA.
Pollak
M
M
Hebert
S C
SC
D000818:Animals; D002118:Calcium / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry*; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000502:physiology*; D009154:Mutation; D010280:Parathyroid Glands / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
D011956:Receptors, Cell Surface; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium