title: A recombinant calcitonin receptor independently stimulates 3',5'-cyclic adenosine monophosphate and Ca2+/inositol phosphate signaling pathways.
abstract: Calcitonin (CT), a polypeptide hormone, regulates calcium homeostasis by activating surface receptors coupled to stimulation of adenylyl cyclase in bone and kidney cells. CT has also been reported to increase cytoplasmic Ca2+ in osteoclasts and renal tubule cells. Signaling pathways activated by a recombinant porcine renal calcitonin receptor transiently expressed in HEK-293 cells were studied. In cells expressing the recombinant CT receptor, salmon CT stimulated cAMP accumulation (EC50, 0.16 nM) and synthesis of inositol phosphates (IP; EC50, 3.7 nM). Two other recombinant receptors, the m1-muscarinic acetylcholine receptor and the LH receptor, activated synthesis of either IP or cAMP, respectively, but not both. Stable expression of the CT receptor in a CT receptor-deficient cell line, M18, restored the cells' ability to increase cytoplasmic Ca2+ in response to salmon CT. These results show that a single recombinant CT receptor can independently activate effector pathways mediated by cAMP and IP/Ca2+.
authors.affiliation: Department of Pharmacology, University of California, San Francisco 94113.
authors.forename: O
authors.initials: O
authors.lastname: Chabre
authors.forename: B R
authors.initials: BR
authors.lastname: Conklin
authors.forename: H Y
authors.initials: HY
authors.lastname: Lin
authors.forename: H F
authors.initials: HF
authors.lastname: Lodish
authors.forename: E
authors.initials: E
authors.lastname: Wilson
authors.forename: H E
authors.initials: HE
authors.lastname: Ives
authors.forename: L
authors.initials: L
authors.lastname: Catanzariti
authors.forename: B A
authors.initials: BA
authors.lastname: Hemmings
authors.forename: H R
authors.initials: HR
authors.lastname: Bourne
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D010957:Plasmids; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D007295:Inositol Phosphates; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D002116:Calcitonin; D000242:Cyclic AMP; D002118:Calcium