MAINTENANCE of a stable internal environment within complex organisms
requires specialized cells that sense changes in the extracellular con
centration of specific ions (such as Ca2+). Although the molecular nat
ure of such ion sensors is unknown, parathyroid cells possess a cell s
urface Ca2+-sensing mechanism that also recognizes trivalent and polyv
alent cations (such as neomycin) and couples by changes in phosphoinos
itide turnover and cytosolic Ca2+ to regulation of parathyroid hormone
secretion1-4. The latter restores normocalcaemia by acting on kidney
and bone2. We now report the cloning of complementary DNA encoding an
extracellular Ca2+-sensing receptor from bovine parathyroid with pharm
acological and functional properties nearly identical to those of the
native receptor. The novel approximately 120K receptor shares limited
similarity with the metabotropic glutamate receptors5 and features a l
arge extracellular domain, containing clusters of acidic amino-acid re
sidues possibly involved in calcium binding, coupled to a seven-membra
ne-spanning domain like those in the G-protein-coupled receptor superf
amily.