Molecular cloning of two receptors from rat brain with high affinity for salmon calcitonin

Albrandt, Keith; Mull, Emily; Brady, Elize M. G.; Herich, John; Moore, Candace X.; Beaumont, Kevin

doi:10.1016/0014-5793(93)81078-e

Cited by 100 publications

(56 citation statements)

References 40 publications

(3 reference statements)

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“…The cloning of mouse and rat brain CTR cDNAs identified another receptor form that contained a predicted nonhomologous 37-amino acid insert in the second extracellular domain, as well as a form homologous to the original porcine kidney cell receptor (11,29,30). Different binding affinities were noted for these two rodent receptor forms (29,30). These observations have confirmed the existence of multiple CTR forms (isoforms) in a single species.…”

mentioning

confidence: 99%

Expression of two human skeletal calcitonin receptor isoforms cloned from a giant cell tumor of bone. The first intracellular domain modulates ligand binding and signal transduction.

Gorn

Rudolph²,

Flannery³

et al. 1995

J. Clin. Invest.

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Two distinct calcitonin (CT) receptor (CTR)-encoding cDNAs (designated GC-2 and GC-10) were cloned and characterized from giant cell tumor of bone (GCT). Both GC-2 and GC-10 differ structurally from the human ovarian cell CTR (o-hCTR) that we cloned previously, but differ from each other only by the presence (GC-10) or absence (GC-2) of a predicted 16-amino acid insert in the putative first intracellular domain. Expression of all three CTR isoforms in COS cells demonstrated that GC-2 has a lower binding affinity for salmon (s) CT (Kd -15 nM) than GC-10 or o-hCTR (Kd -1.5 nM). Maximal stimulatory concentrations of CT resulted in a mean accumulation of cAMP in GC-2 transfected cells that was greater than eight times higher than in cells transfected with GC-10 after normalizing for the number of receptor-expressing cells. The marked difference in maximal cAMP response was also apparent after normalizing for receptor number. GC-2 also demonstrated a more potent ligand-mediated cAMP response compared with GC-10 for both human (h) and sCT (the EC5, values for GC-2 were -0.2 nM for sCT and -2 nM for hCT; EC50 values for GC-10 were -6 nM for sCT and 25 nM for hCT). Reverse transcriptase PCR of GCT RNA indicated that GC-2 transcripts are more abundant than those encoding for GC-10. In situ hybridization on GCT tissue sections demonstrated CTR mRNA expression in osteoclast-like cells. We localized the human CTR gene to chromosome 7 in band q22. The distinct functional characteristics of GC-2 and GC-10, which differ in structure only in the first intracellular domain, indicate that the first intracellular domain of the CTR plays a previously unidentified role in modulating ligand binding and signal transduction via the G protein/adenylate cyclase system. (J. Clin. Invest. 1995. 95:2680-2691

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mentioning

confidence: 99%

Expression of two human skeletal calcitonin receptor isoforms cloned from a giant cell tumor of bone. The first intracellular domain modulates ligand binding and signal transduction.

Gorn

Rudolph²,

Flannery³

et al. 1995

J. Clin. Invest.

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“…sCT on 17b-estradiol secretion progesterone and GnRH-stimulated pituitary LH has also been reported (Tsai et al 1999). Moreover, receptors of CT-designated C1a and C1b receptors have been identified in rat brains (Sexton & Hilton 1992, Albrandt et al 1993. All these studies indicate a physiological role for CT at the pituitary and ovarian levels in mammals.…”

Section: Discussionmentioning

confidence: 77%

Stimulation of salmon calcitonin on secretion of 17β-estradiol by the ovarian follicles of common carp, Cyprinus carpio

Paul

Mukherjee²,

Pramanick³

et al. 2007

Journal of Endocrinology

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The effects of salmon calcitonin (sCT) on the secretion of 17b-estradiol (E 2 ) were examined in female common carp, Cyprinus carpio. Vitellogenic stage fish adapted to high-Ca water were i.p. injected with vehicle, sCT, human chorionic gonadotropin (hCG), or hCG plus sCT. To determine whether ovarian follicles are equipped with CT receptors, a CT binding assay was conducted. In the in vitro experiments, vitellogenic follicles were incubated with stimulators and inhibitors. Administration of sCT increased the basal and hCG-stimulated E 2 release in vivo and in vitro. Binding characteristics of [ 125 I]sCT to plasma membrane preparation of carp ovarian follicles showed saturability with high-affinity (K d Z48 . 48 pmol/l and B max Z1 . 2 pmol/mg protein). To clarify the mechanism of E 2 production by sCT, in vitro effect of sCT and hCG on aromatase activity (conversion of testosterone to E 2 ) and cytochrome P450 aromatase (P450arom) gene expression in carp ovarian follicles were investigated. Salmon CT-stimulated both aromatase activity and P450arom gene expression in ovarian follicles of carp. sCT-stimulated E 2 release by the ovarian follicles in vitro was augmented in the presence of dibutyryl cAMP. Inhibitor of protein kinase A (PKA), SQ 22536 inhibited sCT-stimulated steroid production in a dose-dependent manner. Specific inhibitor of protein kinase C (PKC), NPC-15437 dihydrochloride had no inhibitory effects on sCT-induced E 2 release. The present study indicates that sCT binds specifically to carp ovary and stimulates E 2 production by increasing the activity of cytochrome P450 aromatase and P450arom gene expression. The results further suggest that stimulatory action of sCTon E 2 production is mediated through cAMP pathway.

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“…Inhibition of sCT on secretion of progesterone and GnRH-stimulated pituitary LH has also been reported (Tan et al, 1994). Moreover, receptors of CT-designated C1a and C1b receptors have been identified in rat brain (Sexton and Hilton, 1992;Albrandt et al, 1993). All these information indicates a physiological role of CT at pituitary and ovarian levels in mammals.…”

Section: Discussionmentioning

confidence: 85%

Calcitonin Functions Both as a Hypocalcemic Hormone and Stimulator of Steroid Production and Oocyte Maturation in Ovarian Follicles of Common Carp, Cyprinus carpio

Mukherjee¹,

Kundu²,

Pramanick³

et al. 2011

Update on Mechanisms of Hormone Action - Focus on Metabolism, Growth and Reproduction

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Molecular cloning of two receptors from rat brain with high affinity for salmon calcitonin

Cited by 100 publications

References 40 publications

Expression of two human skeletal calcitonin receptor isoforms cloned from a giant cell tumor of bone. The first intracellular domain modulates ligand binding and signal transduction.

Expression of two human skeletal calcitonin receptor isoforms cloned from a giant cell tumor of bone. The first intracellular domain modulates ligand binding and signal transduction.

Stimulation of salmon calcitonin on secretion of 17β-estradiol by the ovarian follicles of common carp, Cyprinus carpio

Calcitonin Functions Both as a Hypocalcemic Hormone and Stimulator of Steroid Production and Oocyte Maturation in Ovarian Follicles of Common Carp, Cyprinus carpio

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