AMY<sub>2</sub> receptor | Calcitonin receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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AMY2 receptor

Target not currently curated in GtoImmuPdb

Target id: 45

Nomenclature: AMY2 receptor

Family: Calcitonin receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Quaternary Structure: Subunits
RAMP2 (Accessory protein)
CT receptor
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the extracellular domain of human RAMP2.
Resolution:  2.05Å
Species:  Human
References:  10
Natural/Endogenous Ligands
adrenomedullin {Sp: Human}
adrenomedullin 2/intermedin {Sp: Human} , adrenomedullin 2/intermedin {Sp: Mouse} , adrenomedullin 2/intermedin {Sp: Rat}
amylin {Sp: Human} , amylin {Sp: Mouse, Rat}
calcitonin {Sp: Human} , calcitonin {Sp: Mouse, Rat}
α-CGRP {Sp: Human}
β-CGRP {Sp: Human} , β-CGRP {Sp: Mouse}
α-CGRP {Sp: Mouse, Rat}
β-CGRP {Sp: Rat}
Comments: Amylin is the most potent endogenous agonist
Potency order of endogenous ligands (Human)
Poorly defined

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Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
calcitonin {Sp: Human} Hs Full agonist 11.4 pEC50 1
pEC50 11.4 [1]
adrenomedullin {Sp: Human} Hs Full agonist 9.2 pEC50 8
pEC50 9.2 [8]
amylin {Sp: Mouse, Rat} Hs Full agonist 8.5 – 9.9 pEC50 1,3,7
pEC50 8.5 – 9.9 (EC50 3.388x10-9 – 1.25x10-10 M) [1,3,7]
pramlintide Hs Agonist 8.6 – 8.9 pEC50 3
pEC50 8.6 – 8.9 (EC50 2.29x10-9 – 1.38x10-9 M) [3]
Description: Measuring ligand-induced cAMP production in COS and HEK293 cells.
amylin {Sp: Human} Hs Full agonist 8.3 – 9.1 pEC50 3
pEC50 8.3 – 9.1 (EC50 5.37x10-9 – 7.76x10-10 M) [3]
Description: Measuring ligand-induced cAMP production in COS and HEK293 cells.
Tyr0α-CGRP (human) Hs Full agonist 8.3 pEC50 7
pEC50 8.3 [7]
α-CGRP {Sp: Human} Hs Full agonist 6.2 – 9.7 pEC50 5,7-8
pEC50 6.2 – 9.7 [5,7-8]
adrenomedullin 2/intermedin {Sp: Human} Hs Full agonist 6.0 pEC50 6
pEC50 6.0 [6]
Agonist Comments
The AMY2 receptor is a heterodimeric complex of the calcitonin receptor and RAMP2 [9]]. The variability in potency values reported is likely to reflect cell background such as the presence of other endogenous RAMPs and the calcitonin receptor-like receptor [11]. 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.
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  5,7-8
Tissue Distribution
Lung > fundus (stomach) > spleen, brainstem, hypothalamus > liver, cortex, cerebellum.
Note: At present there is virtually no information on the co-localisation of CT with RAMP2. This data is based on the binding of [125I]-amylin and so is an aggregate for AMY1, AMY2 and AMY3 receptors.
Species:  Rat
Technique:  Radioligand binding.
References:  2
Functional Assays
Measurement of cAMP levels in HEK 293 cells transfected with AMY2 receptors (CT receptor plus RAMP2).
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  cAMP accumulation.
References:  7-8
Biologically Significant Variants
Type:  Splice variants
Species:  Human
Description:  AMY2 receptors are formed by the interaction of RAMP2 with the CT receptor and its splice 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.
References:  4,11


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1. Armour SL, Foord S, Kenakin T, Chen WJ. (1999) Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor. J Pharmacol Toxicol Methods, 42 (4): 217-24. [PMID:11033437]

2. Bhogal R, Smith DM, Bloom SR. (1992) Investigation and characterization of binding sites for islet amyloid polypeptide in rat membranes. Endocrinology, 130 (2): 906-13. [PMID:1310282]

3. Gingell JJ, Burns ER, Hay DL. (2014) Activity of pramlintide, rat and human amylin but not Aβ1-42 at human amylin receptors. Endocrinology, 155 (1): 21-6. [PMID:24169554]

4. Gorn AH, Rudolph SM, Flannery MR, Morton CC, Weremowicz S, Wang TZ, Krane SM, Goldring SR. (1995) 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. J Clin Invest., 95: 2680-2691. [PMID:7769107]

5. Hay DL, Christopoulos G, Christopoulos A, Poyner DR, Sexton PM. (2005) Pharmacological discrimination of calcitonin receptor: receptor activity-modifying protein complexes. Mol. Pharmacol., 67 (5): 1655-65. [PMID:15692146]

6. Hong Y, Hay DL, Quirion R, Poyner DR. (2012) The pharmacology of adrenomedullin 2/intermedin. Br. J. Pharmacol., 166 (1): 110-20. [PMID:21658025]

7. Kuwasako K, Cao YN, Nagoshi Y, Tsuruda T, Kitamura K, Eto T. (2004) Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins. Mol. Pharmacol., 65 (1): 207-13. [PMID:14722252]

8. Kuwasako K, Kitamura K, Nagoshi Y, Eto T. (2003) Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from co-expression of calcitonin receptor with receptor activity-modifying proteins. Biochem. Biophys. Res. Commun., 301 (2): 460-4. [PMID:12565884]

9. Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, Foord SM. (2002) International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol. Rev., 54 (2): 233-46. [PMID:12037140]

10. Quigley A, Pike ACW, Burgess-Brown N, Krojer T, Shrestha L, Goubin S, Kim J, Das S, Muniz JRC, Canning P, Chaikuad A, Vollmar M, Von Delft F, Arrowsmith CH, Weigelt J, Edwards AM, Bountra C, Barr AJ, Carpenter EP. Structure of the Extracellular Domain of Human Ramp2. Accessed on 20/07/2012. Modified on 20/07/2012. PDB,

11. Tilakaratne N, Christopoulos G, Zumpe ET, Foord SM, Sexton PM. (2000) Amylin receptor phenotypes derived from human calcitonin receptor/RAMP coexpression exhibit pharmacological differences dependent on receptor isoform and host cell environment. J. Pharmacol. Exp. Ther., 294 (1): 61-72. [PMID:10871296]


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