A recombinant human calcitonin receptor functions as an extracellular calcium sensor.
Calcitonin, a peptide hormone active in calcium homeostasis, is used in the treatment of bone loss disorders because it inhibits osteoclast function. A human calcitonin receptor was cloned and expressed in baby hamster kidney cells. Three independent stable transfectants respond to calcitonin via increased intracellular calcium ([Ca2+]i) and cyclic adenosine 3',5'-monophosphate (cAMP). We made the interesting observation that these cells also respond to millimolar increases in extracellular calcium via a rapid and sustained elevation in [Ca2+]i, whereas three calcitonin receptor-negative baby hamster kidney cell lines, two of which express recombinant receptors related to the calcitonin receptor, show no sensitivity to changes in extracellular calcium. The increase of [Ca2+]i in response to both calcitonin and extracellular calcium is a function of the average number of calcitonin receptors per cell. These studies suggest a dual role for the calcitonin receptor as a hormone receptor and an extracellular calcium sensor.
Stroop
S D
SD
ZymoGenetics, Inc., Seattle, Washington 98105.
Thompson
D L
DL
Kuestner
R E
RE
Moore
E E
EE
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002116:Calcitonin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D007668:Kidney; D007700:Kinetics; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002116:Calcitonin; D005934:Glucagon; D000242:Cyclic AMP; D002118:Calcium