{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T13:16:59Z","timestamp":1747747019732,"version":"3.37.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1995,4,1]],"date-time":"1995-04-01T00:00:00Z","timestamp":796694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Stable transfectants expressing a recombinant human calcitonin receptor respond to calcitonin via increased cyclic adenosine 3\u2032,5\u2032 monophosphate (cAMP, EC50 = 0.06 nM salmon calcitonin [sCT]) and a transient mobilization of intracellular calcium ([Ca2+]i) coincident with turnover of inositol phosphate (IP; EC50 = 6 nM sCT). Millimolar increases in extracellular calcium ([Ca2+]o, EC50 = 8 mM) cause a rapid elevation in [Ca2+]i after a calcitonin dose-dependent pretreatment of cells (pretreatment EC50 = 0.2 nM sCT). Cells exhibit persistent sensitivity to increased [Ca2+]o up to 3 h after hormone exposure and even after multiple cycles of increased [Ca2+]o followed by wash. Calcitonin pretreatment of cells also allows apparent influx of elevated extracellular strontium and manganese, but little or no effect is observed on addition of barium, cadmium, or lanthanum. Human amylin (100 nM) causes a rapid and transient increase in [Ca2+]i comparable to that of calcitonin; however, no significant response to increased [Ca2+]o is observed after amylin addition. Human calcitonin gene-related product (hCGRP) (300 nM) and forskolin do not increase [Ca2+]i or activate a sensitivity to increased [Ca2+]o. Nevertheless, human amylin and human calcitonin gene-related product (hCGRP) activate adenylate cyclase with EC50s of 0.7 nM and 8 nM, respectively. The calcium-channel drugs verapamil, BAY K 8644, diltiazem, and nifedipine have little effect on [Ca2+]i increases. The calcitonin-induced transient mobilization of calcium is inhibited by treatment of cells with cholera toxin or 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8); whereas, the response to subsequent increased [Ca2+]o is inhibited by lanthanum chloride (200 \u03bcM) and lower pH (6.0). These studies suggest that a recombinant human calcitonin receptor activates three unique signal transduction pathways in BHK cells. Subnanomolar calcitonin persistently activates adenylate cyclase and a novel pathway coupled to calcium influx while much higher calcitonin levels increase inositol phosphate turnover and generate a transient mobilization of [Ca2+]i stores.<\/jats:p>","DOI":"10.1002\/jbmr.5650100404","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T16:07:00Z","timestamp":1265213220000},"page":"524-532","source":"Crossref","is-referenced-by-count":10,"title":["Intracellular calcium increases mediated by a recombinant human calcitonin receptor"],"prefix":"10.1093","volume":"10","author":[{"given":"Steven D.","family":"Stroop","sequence":"first","affiliation":[{"name":"ZymoGenetics, Inc., Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma E.","family":"Moore","sequence":"additional","affiliation":[{"name":"ZymoGenetics, Inc., Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1995,4,1]]},"reference":[{"volume-title":"Calcitonin. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism","year":"1993","author":"Deftos","key":"2024013114203587100_bib1"},{"key":"2024013114203587100_bib2","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1126\/science.2983422","article-title":"Interaction of calcitonin and calcitonin gene-related peptide at receptor sites in target tissues.","volume":"227","author":"Goltzman","year":"1985","journal-title":"Science"},{"key":"2024013114203587100_bib3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/1043-2760(93)90071-L","article-title":"Receptors for secretin, calcitonin, parathyroid hormone\/PTH-related peptide, vasoactive intestinal peptide, glucagonlike peptide 1, growth hormone-releasing hormone, and glucagon belong to a newly discovered g-protein linked receptor family.","volume":"4","author":"Segre","year":"1993","journal-title":"Trends Endocrinol Metab"},{"key":"2024013114203587100_bib4","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1172\/JCI116046","article-title":"Cloning, characterization, and expression of a human calcitonin receptor from an ovarian carcinoma cell line.","volume":"90","author":"Corn","year":"1992","journal-title":"J Clin Invest"},{"key":"2024013114203587100_bib5","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S0026-895X(25)09678-6","article-title":"Cloning and characterization of an abundant subtype of the human calcitonin receptor.","volume":"46","author":"Kuestner","year":"1994","journal-title":"Mol Pharm"},{"key":"2024013114203587100_bib6","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/366575a0","article-title":"Cloning and characterization of an extracellular calcium-sensing receptor from bovine parathyroid.","volume":"366","author":"Brown","year":"1993","journal-title":"Nature"},{"key":"2024013114203587100_bib7","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/BF01116610","article-title":"\u201cCalcium receptors\u201d on eukaryotic cells with special reference to the osteoclast.","volume":"10","author":"Zaidi","year":"1990","journal-title":"Biosci Rep"},{"key":"2024013114203587100_bib8","doi-asserted-by":"crossref","first-page":"14342","DOI":"10.1016\/S0021-9258(18)71683-9","article-title":"Control of cytosolic free calcium in rat and chicken osteoclasts.","volume":"264","author":"Malgaroli","year":"1989","journal-title":"J Biol Chem"},{"key":"2024013114203587100_bib9","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/0006-291X(92)90527-R","article-title":"Is the osteoclast calcium \u201creceptor\u201d a receptor operated calcium channel?","volume":"183","author":"Bax","year":"1992","journal-title":"Biochem Biophys Res Commun"},{"key":"2024013114203587100_bib10","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/0014-4827(88)90191-7","article-title":"Microelectrode studies on the acid microenvironment beneath adherent macrophages and osteoclasts.","volume":"175","author":"Silver","year":"1988","journal-title":"Exp Cell Res"},{"key":"2024013114203587100_bib11","doi-asserted-by":"crossref","first-page":"19927","DOI":"10.1016\/S0021-9258(20)80674-7","article-title":"A recombinant human calcitonin receptor functions as an extracellular calcium sensor.","volume":"268","author":"Stroop","year":"1993","journal-title":"J Biol Chem"},{"key":"2024013114203587100_bib12","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1210\/endo.135.1.8013352","article-title":"Isoforms of the rat calcitonin receptor: consequences for ligand binding and signal transduction.","volume":"135","author":"Houssami","year":"1994","journal-title":"Endocrinology"},{"key":"2024013114203587100_bib13","first-page":"551","article-title":"A recombinant calcitonin receptor independently stimulates cAMP and Ca\/IP3 signaling pathways.","volume":"6","author":"Chabre","year":"1992","journal-title":"Mol Endocrinol"},{"key":"2024013114203587100_bib14","first-page":"F1110","article-title":"A cloned renal calcitonin receptor couples to adenylyl cyclase and phospholipase C.","volume":"262","author":"Force","year":"1992","journal-title":"Am J Physiol"},{"key":"2024013114203587100_bib15","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1042\/bj1960513","article-title":"Calcitonin binding and degradation by two cultured human breast cancer cells lines.","volume":"196","author":"Findlay","year":"1981","journal-title":"Biochem J"},{"key":"2024013114203587100_bib16","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of Ca indicators with greatly improved fluorescence properties.","volume":"260","author":"Grynkiewicz","year":"1985","journal-title":"J Biol Chem"},{"year":"1991","author":"Thomas","key":"2024013114203587100_bib17"},{"key":"2024013114203587100_bib18","first-page":"129","article-title":"Mechanisms of calcitonin induction of prolonged activation of adenylate cyclase in human cancer cells.","volume":"9","author":"Michealangeli","year":"1983","journal-title":"J Cyclic Nucl Protein Phos Res"},{"key":"2024013114203587100_bib19","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1073\/pnas.90.7.3068","article-title":"Calcium and manganese influx through receptor-mediated activation of nonspecific cation channels in mast cells.","volume":"90","author":"Fasolato","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013114203587100_bib20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/1043-2760(93)90095-V","article-title":"Amylin in bone conservation.","volume":"4","author":"Zaidi","year":"1993","journal-title":"Trends Endocrinol Metab"},{"first-page":"343","year":"1974","author":"Weiss","key":"2024013114203587100_bib21"},{"key":"2024013114203587100_bib22","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0968-0004(92)90005-T","article-title":"G proteins.","volume":"17","author":"Hepler","year":"1992","journal-title":"Trends Biochem Sci"},{"key":"2024013114203587100_bib23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/jcp.1041530103","article-title":"Mechanism of action of amylin in bone.","volume":"153","author":"Tamura","year":"1992","journal-title":"J Cell Physiol"},{"key":"2024013114203587100_bib24","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0165-6147(94)90282-8","article-title":"Receptor-activated calcium influx: how many mechanisms for how many channels?","volume":"15","author":"Fasolato","year":"1994","journal-title":"Trends Pharm Sci"},{"key":"2024013114203587100_bib25","doi-asserted-by":"crossref","first-page":"9651","DOI":"10.1016\/S0021-9258(17)36931-4","article-title":"Characterization of the substance P receptor-mediated calcium influx in cDNA transfected Chinese hamster ovary cells.","volume":"269","author":"Mochizuki-Oda","year":"1994","journal-title":"J Biol Chem"},{"key":"2024013114203587100_bib26","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.ph.52.030190.001213","article-title":"Ionic channels and their regulation by G-protein subunits.","volume":"52","author":"Brown","year":"1990","journal-title":"Annu Rev Physiol"},{"key":"2024013114203587100_bib27","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0014-5793(90)81290-5","article-title":"Receptor-mediated calcium entry.","volume":"268","author":"Rink","year":"1990","journal-title":"FEBS Lett"},{"key":"2024013114203587100_bib28","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1073\/pnas.83.3.654","article-title":"Effects of external pH on calcium channels: experimental studies and theoretical considerations using a two-site, two-ion model.","volume":"83","author":"Iljima","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013114203587100_bib29","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/BF00232904","article-title":"Effects of extracellular calcium and protons on osteoclast potassium currents.","volume":"140","author":"Arkett","year":"1994","journal-title":"J Membrane Biol"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.5650100404","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/10\/4\/524\/56499760\/5650100404.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/10\/4\/524\/56499760\/5650100404.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T08:53:01Z","timestamp":1739782381000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/10\/4\/524-532\/7500818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,4,1]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[1995,4,1]]},"published-print":{"date-parts":[[1995,4,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.5650100404","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"type":"print","value":"0884-0431"},{"type":"electronic","value":"1523-4681"}],"subject":[],"published-other":{"date-parts":[[1995,4,1]]},"published":{"date-parts":[[1995,4,1]]}}}