AMY<sub>1</sub> receptor | Calcitonin receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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AMY1 receptor

Target not currently curated in GtoImmuPdb

Target id: 44

Nomenclature: AMY1 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
RAMP1 (Accessory protein)
CT receptor
Previous and Unofficial Names
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the extracellular domain of human RAMP1
PDB Id:  2YX8
Resolution:  2.4Å
Species:  Human
References:  9
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, α-CGRP, and β-CGRP are the most potent endogenous agonists
Potency order of endogenous ligands (Human)
calcitonin (salmon)amylin (IAPP, P10997) ≥ α-CGRP (CALCA, P06881), β-CGRP (CALCB, P10092) > adrenomedullin 2/intermedin (ADM2, Q7Z4H4) ≥ calcitonin (CALCA, P01258) > adrenomedullin (ADM, P35318)

Download all structure-activity data for this target as a CSV file

Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]αCGRP (human) Hs Agonist 9.0 – 10.0 pKd
pKd 9.0 – 10.0
calcitonin (salmon) Rn Full agonist 9.0 pKi 3
pKi 9.0 [3]
calcitonin {Sp: Human} Hs Full agonist 8.9 – 11.3 pEC50 1,7,13
pEC50 8.9 – 11.3 [1,7,13]
amylin {Sp: Mouse, Rat} Hs Full agonist 9.0 – 10.7 pEC50 1,5,7,10
pEC50 9.0 – 10.7 (EC50 1.047x10-9 – 1.99x10-11 M) [1,5,7,10]
α-CGRP {Sp: Human} Hs Full agonist 8.7 – 10.8 pEC50 7,10-11,13,20
pEC50 8.7 – 10.8 [7,10-11,13,20]
pramlintide Hs Agonist 9.4 – 9.4 pEC50 5
pEC50 9.4 – 9.4 (EC50 4.36x10-10 – 3.55x10-10 M) [5]
Description: Measuring ligand-induced cAMP production in COS and HEK293 cells.
amylin {Sp: Human} Hs Full agonist 9.0 – 9.7 pEC50 5
pEC50 9.0 – 9.7 (EC50 1x10-9 – 1.94x10-10 M) [5]
Description: Measuring ligand-induced cAMP production in COS and HEK293 cells.
β-CGRP {Sp: Human} Hs Full agonist 9.2 pEC50 7
pEC50 9.2 [7]
Tyr0α-CGRP (human) Hs Full agonist 7.6 – 9.5 pEC50 7,10
pEC50 7.6 – 9.5 [7,10]
[Cys(Et)2,7]α-CGRP (human) Hs Full agonist 7.8 – 8.4 pEC50 7,10
pEC50 7.8 – 8.4 [7,10]
adrenomedullin 2/intermedin {Sp: Human} Hs Full agonist 8.0 pEC50 8
pEC50 8.0 [8]
adrenomedullin {Sp: Human} Hs Full agonist 6.5 – 8.4 pEC50 7,11
pEC50 6.5 – 8.4 [7,11]
β-CGRP {Sp: Human} Hs - - -
View species-specific agonist tables
Agonist Comments
The AMY1 receptor is a heterodimeric complex of the calcitonin receptor and RAMP1 [15]. 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 [18]. 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.
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
α-CGRP-(8-37) (human) Hs Antagonist 6.6 pKB 7
pKB 6.6 [7]
olcegepant Hs Antagonist 7.2 pKd 20
pKd 7.2 [20]
AC187 Hs Antagonist 8.0 pKi 7
pKi 8.0 [7]
CT-(8-32) (salmon) Hs Antagonist 7.8 pKi 7
pKi 7.8 [7]
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  3,7,10-11,13,15
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 RAMP1. 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 COS-7 cells transfected with AMY1 receptors (CT receptor plus RAMP1).
Species:  Human
Tissue:  COS-7 cells.
Response measured:  cAMP accumulation.
References:  3,7
Physiological Functions
Amylin inhibits [14C]glycogen accumulation in isolated skeletal muscle.
Species:  Rat
Tissue:  Ex vivo
References:  4,12
Amylin is a potent inhibitor of gastric emptying.
Species:  Rat
Tissue:  In vivo
References:  21
Amylin reduces food intake (human and rat). The receptor through which this effect occurs is unclear.
Species:  Human
Tissue:  In vivo
References:  14,17
Amylin inhibits glycolysis and increases free radical production and apoptosis. The receptor through which this happens is unclear.
Species:  Mouse
Tissue:  in vivo.
References:  19
Biologically Significant Variants
Type:  Splice variants
Species:  Human
Description:  AMY1 receptors are formed by the interaction of RAMP1 with the calcitonin receptor and its splice variants. The hCT(b) (formerly hCTR1 or CTRI1+) receptor is of identical sequence to the hCT(a) receptor but contains a 16 amino acid insert in the first intracellular loop. When the AMY1 receptor incorporates the delta 47 splice variant of the CTR, the affinity of the receptor for CGRP increases and now exceeds that for amylin.
References:  6,16,18


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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. Christopoulos G, Perry KJ, Morfis M, Tilakaratne N, Gao Y, Fraser NJ, Main MJ, Foord SM, Sexton PM. (1999) Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol. Pharmacol., 56 (1): 235-42. [PMID:10385705]

4. Cooper GJ, Leighton B, Dimitriadis GD, Parry-Billings M, Kowalchuk JM, Howland K, Rothbard JB, Willis AC, Reid KB. (1988) Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle. Proc. Natl. Acad. Sci. U.S.A., 85 (20): 7763-6. [PMID:3051005]

5. 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]

6. 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]

7. 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]

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

9. Kusano S, Kukimoto-Niino M, Akasaka R, Toyama M, Terada T, Shirouzu M, Shindo T, Yokoyama S. (2008) Crystal structure of the human receptor activity-modifying protein 1 extracellular domain. Protein Sci., 17 (11): 1907-14. [PMID:18725456]

10. 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]

11. 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]

12. Leighton B, Cooper GJ. (1988) Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. Nature, 335 (6191): 632-5. [PMID:3050530]

13. Leuthauser K, Gujer R, Aldecoa A, McKinney RA, Muff R, Fischer JA, Born W. (2000) Receptor-activity-modifying protein 1 forms heterodimers with two G-protein-coupled receptors to define ligand recognition. Biochem J., 351: 347-351. [PMID:11023820]

14. Lutz TA. (2006) Amylinergic control of food intake. Physiol. Behav., 89 (4): 465-71. [PMID:16697020]

15. 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]

16. Qi T, Dong M, Watkins HA, Wootten D, Miller LJ, Hay DL. (2013) Receptor activity-modifying protein-dependent impairment of calcitonin receptor splice variant Δ(1-47)hCT((a)) function. Br. J. Pharmacol., 168 (3): 644-57. [PMID:22946511]

17. Roth JD, Erickson MR, Chen S, Parkes DG. (2012) GLP-1R and amylin agonism in metabolic disease: complementary mechanisms and future opportunities. Br. J. Pharmacol., 166 (1): 121-36. [PMID:21671898]

18. 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]

19. Venkatanarayan A, Raulji P, Norton W, Chakravarti D, Coarfa C, Su X, Sandur SK, Ramirez MS, Lee J, Kingsley CV et al.. (2015) IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo. Nature, 517 (7536): 626-30. [PMID:25409149]

20. Walker CS, Eftekhari S, Bower RL, Wilderman A, Insel PA, Edvinsson L, Waldvogel HJ, Jamaluddin MA, Russo AF, Hay DL. (2015) A second trigeminal CGRP receptor: function and expression of the AMY1 receptor. Ann Clin Transl Neurol, 2 (6): 595-608. [PMID:26125036]

21. Young AA, Gedulin B, Vine W, Percy A, Rink TJ. (1995) Gastric emptying is accelerated in diabetic BB rats and is slowed by subcutaneous injections of amylin. Diabetologia, 38 (6): 642-8. [PMID:7672483]


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