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CT

Previous and Unofficial Names
CTR2
CTRI1-
Structural Information
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Name Reference
Human 7 490 7q21.3 CALCR 1
Rat 7 516 4q13 Calcr
Mouse 7 515 6 A1 Calcr 2-3
Contents:
Previous and Unofficial Names
Structural Information
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Biologically Significant Variants
Receptor Comments
Database Links
ChEMBL Target 119 (Hs), 11064 (Rn)
Ensembl ENSG00000004948 (Hs), ENSMUSG00000023964 (Mm), ENSRNOG00000010053 (Rn)
Entrez Gene 799 (Hs), 12311 (Mm), 116506 (Rn)
GeneCards CALCR (Hs)
HomoloGene 1320 (Hs)
OMIM 114131 (Hs)
PharmGKB Gene PA26032 (Hs)
RefSeq Nucleotide NM_001742 (Hs), NM_007588 (Mm), NM_053816 (Rn), NM_001034015 (Rn)
RefSeq Protein NP_001733 (Hs), NP_031614 (Mm), NP_446268 (Rn), NP_001029187 (Rn)
UniGene Hs. 489127 (Hs)
UniProt P30988 (Hs), Q60755 (Mm), P32214 (Rn)
Wikipedia CT
Search for 3D structures on the PDB
Search using keywords: Calcitonin receptors CT Search using accession numbers: P32214 || P30988 || Q60755
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
CT (human) Hs Full agonist 9.0 – 11.2 pEC50 10,17,30,33-35
CT (salmon) Hs Full agonist 7.6 – 11.1 pEC50 9,16-17,36
amylin (human) Hs Full agonist 8.0 – 9.2 pEC50 31,34
amylin (rat) Hs Full agonist 7.0 – 9.5 pEC50 10,31,35
α-CGRP (human) Hs Full agonist 6.2 – 8.4 pEC50 10,30-32
AM (human) Hs Full agonist 6.7 – 7.7 pEC50 10,33
β-CGRP (human) Hs Full agonist 7.2 pEC50 10
AM2/intermedin short Hs Full agonist 6.5 pEC50 10
Agonist Comments
This receptor interacts with RAMPs to form several subtypes of high affinity amylin receptor [4] (see receptor comments below) which also have significant affinity for CGRP [5]. The variability in potency values reported is likely to reflect cell background such as the presence of endogenous RAMPs. It is difficult to ascertain the contribution of such factors to the reported values.

Human amylin is rarely used because of its propensity to aggregate.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
CT (8-32) (salmon) Hs Antagonist 8.17 pKi 10
AC187 Hs Antagonist 7.15 pKi 10
CT (8-32) (salmon) Hs Antagonist 9.0 pIC50 37

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Comments:  The insert positive human calcitonin receptor (hCT(b)) has reduced signalling capacity. Inhibition of bone resorption by CT has been shown to be PKA dependent.
References:  7,9-10
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  The insert positive human calcitonin receptor (hCT(b)) has reduced signalling capacity. CT appears to stimulate this pathway in pituitary folliculo-stellate cells and hepatocytes.
References:  7,11-13
Tissue Distribution
Brain: Most abundant in the nucleus accumbens, lateral arcuate nucleus, lateral substantia nigra, bed nucleus of the stria terminalis, locus coeruleus, area postrema, nucleus of the solitary tract, and some of the nuclei of the reticular formation.
Species:  Rat
Technique:  Immunohistochemistry.
References:  23
Testes.
Species:  Rat
Technique:  Radioligand binding.
References:  24-25
Brain: lateral and medial preoptic area, dorso-medial aspect of the suprachiasmic nucleus, paraventricular nucleus of the hypothalamus, arcuate nucleus, nucleus accumbens, medial nucleus of the amygdala, locus coeruleus > raphe nucleus, olfactory bulb >> pituitary gland.
Species:  Rat
Technique:  in situ hybridisation.
References:  26
Stomach, duodenum, jejunum, kidney, bone.
Species:  Rat
Technique:  Radioligand binding.
References:  27
Functional Assays
Measurement of cAMP levels in COS-7 cells transfected with the CT receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  cAMP accumulation.
References:  9-10
Physiological Functions
Calcitonin is a potent inhibitor of bone resorption acting directly on osteoclasts.
Species:  Mouse
Tissue:  Bone.
References:  28
Calcitonin inhibits food intake when injected into hypothalamic areas known to be rich in calcitonin receptors.
Species:  Human
Tissue:  In vivo.
References:  29
Physiological Consequences of Altering Gene Expression
Global deletion of exons 6 and 7 of calcr results in embryonic death prior to initiation of skeletogenesis. calcr+/-mice have a high bone mass phenotype due to increased bone formation.
Species:  Mouse
Tissue: 
Technique:  Knockout
References:  14
A global calcr-deletion model using the Cre-loxP system in which >94% of calcr is deleted displayed mildly increased bone formation under normal conditions. When challenged, however, in calcitriol (1,25(OH)2D3)-induced hypercalcaemia, serum total calcium was greatly increased in the mutant mice, consistent with a regulatory role for calcitonin on bone primarily under conditions of calcium stress.
Species:  Mouse
Tissue: 
Technique:  Knockout
References:  15
Biologically Significant Variants
The human CT(b) (formerly CTR1 or CTRI1+) receptor is of identical sequence to the human CT(a) receptor but contains a 16 amino acid insert in the first intracellular loop. The binding properties of this receptor are similar to the human CT(a) receptor but it is poorly internalised and has altered G-protein coupling. The interaction of this receptor with RAMPs may also be subtly different. Although generally less abundant than the human CT(a) receptor, this splice variant is significantly expressed in the ovary, placenta, bone marrow and lung.
Type:  Splice variants.
Species:  Human
References:  5,16
Variant of the human calcitonin receptor which lacks 47 amino acids at the N-terminus, including a potential glycosylation site and the predicted signal sequence. Although little studied this receptor does not appear to express or function significantly differently to the full length receptor.
Type:  Splice variants.
Species:  Human
References:  17
A naturally occurring variant of the human calcitonin receptor is a T to C base mutation which encodes a leucine447 to proline change. No effect on ligand binding or receptor function has been observed in vitro but the polymorphism is associated with decreased fracture risk in post-menopausal women. The prevalence of the polymorphism differs between ethnic groups.
Type:  Single nucleotide polymorphism.
Species:  Human
References:  18-21
Rat CT(b) receptor. Rat calcitonin receptor that contains a 37 amino acid insert in the first extracellular loop. The insert negative form of the receptor is known as rat CT(a). Similar receptors are found in mouse. The insert reduces affinity for some calcitonin peptides.
Type:  Splice variants.
Species:  Rat
References:  5,22
Receptor Comments
The CT receptor binds to receptor activity modifying proteins (RAMPs) to form high affinity amylin receptors[5], reviewed in [4,6].
CT and RAMP1 make up the AMY1 receptor.
CT and RAMP2 make up the AMY2 receptor.
CT and RAMP3 make up the AMY3 receptor.

As [125I]-calcitonin (salmon) binds with high affinity to calcitonin and amylin receptors, data using this radioligand should be treated with caution.

The presence of CT receptor mRNA does not explain the phenotype of the receptor that is expressed. The expression of RAMP accessory proteins must also be considered.

Calcitonin receptor splice variants may be differentially expressed [7-8].

To cite this receptor data page, please use the following:

Debbie Hay, David R. Poyner.
Calcitonin receptors: CT. Last modified on 2010-06-29. Accessed on 2010-09-09. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=43.


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