Receptors for calcitonin, calcitonin gene related peptide, amylin, and adrenomedullin

1995 ◽  
Vol 73 (7) ◽  
pp. 963-967 ◽  
Author(s):  
Roman Muff ◽  
Walter Born ◽  
Jan A. Fischer
Keyword(s):  
Amino Acid ◽  
Disulfide Bridge ◽  
Calcitonin Gene Related Peptide ◽  
Ring Structure ◽  
Cross Reactivity ◽  
Related Peptide ◽  
C Terminus ◽  
Calcitonin Gene ◽  
G Protein Coupled ◽  
Biological Actions

Calcitonin, calcitonin gene related peptide, amylin, and adrenomedullin are structurally related polypeptides characterized by a six or seven amino acid ring structure linked by a disulfide bridge and an amidated C-terminus. They exhibit overlapping biological actions as a result of cross-reactivity between the different receptors. In this article, the respective receptors and G-protein-coupled postreceptor events are reviewed in relation to some of the biological actions of the peptides.Key words: adrenomedullin, amylin, calcitonin gene related peptide, cyclic AMP, receptors.

Calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin: homologous peptides, separate receptors and overlapping biological actions

1995 ◽  
Vol 133 (1) ◽  
pp. 17-20 ◽  
Author(s):  
Roman Muff ◽  
Walter Born ◽  
Jan A Fischer
Keyword(s):  
Bioactive Peptides ◽  
Disulfide Bridge ◽  
Calcitonin Gene Related Peptide ◽  
G Protein Coupled Receptors ◽  
Calcitonin Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Ring Structures ◽  
G Protein Coupled ◽  
Biological Actions

Muff R, Born W, Fischer JA. Calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin: homologous peptides, separate receptors and overlapping biological actions. Eur J Endocrinol 1995;133:17–20. ISSN 0804–4643 Calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin are structurally related peptides with N-terminal 6–7 amino acid ring structures linked by a disulfide bridge and with amidated C-termini. Among the related bioactive peptides, the structures of the calcitonin receptor and subtypes thereof have been identified so far through molecular cloning. Cross-reaction between receptors of calcitonin, calcitonin gene-related peptide, adrenomedullin and amylin, as well as overlapping biological actions, anticipate that the respective receptors belong to a family of G-protein-coupled receptors that include those of parathyroid hormone, secretin and vasointestinal peptide. Jan A Fischer, Klinik Balgrist, Forchstrasse 340, CH-8008 Zurich, Switzerland

scholarly journals Exploring Ligand Binding to Calcitonin Gene-Related Peptide Receptors

2021 ◽  
Vol 8 ◽  
Author(s):  
Giuseppe Deganutti ◽  
Silvia Atanasio ◽  
Roxana-Maria Rujan ◽  
Patrick M. Sexton ◽  
Denise Wootten ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Ligand Binding ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Approved Drugs ◽  
G Protein Coupled ◽  
Dynamic Docking ◽  
Receptor Family

Class B1 G protein-coupled receptors (GPCRs) are important targets for many diseases, including cancer, diabetes, and heart disease. All the approved drugs for this receptor family are peptides that mimic the endogenous activating hormones. An understanding of how agonists bind and activate class B1 GPCRs is fundamental for the development of therapeutic small molecules. We combined supervised molecular dynamics (SuMD) and classic molecular dynamics (cMD) simulations to study the binding of the calcitonin gene-related peptide (CGRP) to the CGRP receptor (CGRPR). We also evaluated the association and dissociation of the antagonist telcagepant from the extracellular domain (ECD) of CGRPR and the water network perturbation upon binding. This study, which represents the first example of dynamic docking of a class B1 GPCR peptide, delivers insights on several aspects of ligand binding to CGRPR, expanding understanding of the role of the ECD and the receptor-activity modifying protein 1 (RAMP1) on agonist selectivity.

scholarly journals Cross-reactivity of amylin with calcitonin-gene-related peptide binding sites in rat liver and skeletal muscle membranes

1991 ◽  
Vol 277 (1) ◽  
pp. 139-143 ◽  
Author(s):  
A Chantry ◽  
B Leighton ◽  
A J Day
Keyword(s):  
Skeletal Muscle ◽  
Binding Site ◽  
Rat Liver ◽  
Specific Binding ◽  
Calcitonin Gene Related Peptide ◽  
Cross Reactivity ◽  
Scatchard Analysis ◽  
Human Calcitonin ◽  
Related Peptide ◽  
Calcitonin Gene

This study examines whether the high degree of sequence identity between amylin and calcitonin-gene-related peptide (CGRP) is reflected in their cross-reactivity at the level of membrane receptor binding. Rat liver plasma membranes contain a specific saturable binding site for 125I-labelled human CGRP-1. Binding reached equilibrium within 30 min and was rapidly reversed by re-incubating membranes in the presence of 1 microM human CGRP. In addition, the presence of 50 mM- or 500 mM-NaCl lowered specific binding by 30% and 77% respectively. Scatchard analysis was consistent with a single high-affinity site with a dissociation constant (Kd) of 0.125 nM and binding capacity (Bmax.) of 580 fmol/mg of membrane protein. Specific binding of 125I-labelled human CGRP-1 to both liver and skeletal muscle membranes was inhibited by human CGRP-1 [IC50 (concn. causing half-maximal inhibition of binding) 0.1-0.3 nM], and rat amylin (IC50 10 nM), but not by human calcitonin. Covalent cross-linking of 125I-CGRP to its binding site in rat skeletal muscle and liver membranes resulted in labelling of a major species of about 70 kDa under reducing conditions and about 55 kDa under alkylating conditions, as visualized on SDS/PAGE. These radiolabelled species were absent in the presence of CGRP or amylin at 1 microM. These results are indicative of a common binding site for both CGRP and amylin in liver and skeletal muscle, and it is suggested that both peptides mediate their actions through the same effector system. The normal physiological importance and the relevance to the pathology of type 2 diabetes of these data are discussed.

Cellular distribution of PACAP-38 and PACAP receptors in the rat brain: Relation to migraine activated regions

Cephalalgia ◽  
2019 ◽  
Vol 40 (6) ◽  
pp. 527-542 ◽  
Author(s):  
Karin Warfvinge ◽  
Lars Edvinsson
Keyword(s):  
Amino Acid ◽  
Rat Brain ◽  
Vasoactive Intestinal Polypeptide ◽  
Calcitonin Gene Related Peptide ◽  
Amino Acid Sequences ◽  
Primary Headaches ◽  
Functional Responses ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Intestinal Polypeptide

Background Pituitary adenylate cyclase-activating polypeptide (PACAP) occurs as either a 27- or 38-amino acid neuropeptide and belongs to the vasoactive intestinal polypeptide/glucagon/secretin family of peptides. PACAP and vasoactive intestinal polypeptide have a 68% homology of their amino acid sequences and share three B-type G-protein coupled receptors: VPAC1, VPAC2 and PAC1 receptors. Methods/results The distribution of PACAP-38 and its receptors in the brain is only partly described in the literature. Here, we have performed a study to provide the more general picture of this system in rat brain in order to understand a putative role in primary headaches and partly in relation to the calcitonin gene-related peptide system. We observed a rich expression of PACAP-38 and PAC1 receptor immunoreactivity in many regions throughout the cerebrum, cerebellum and brainstem. The expression pattern points to multiple functions, not least associated with pain and reactions to pain. The expression of VPAC1 and VPAC2 receptor immunoreactivity was very sparse. In several regions such as the cerebral cortex, trigeminal nucleus caudalis, hypothalamus and pons there was a close relation to calcitonin gene-related peptide expression. Conclusion The findings suggest that the rich supply of PACAP-38 and PAC1 receptors is associated with basic functional responses in the central nervous system (CNS), and there are important close anatomical relations with calcitonin gene-related peptide in CNS regions associated with migraine pathophysiology.

scholarly journals Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies

2013 ◽  
Vol 10 (79) ◽  
pp. 20120846 ◽  
Author(s):  
Shabana Vohra ◽  
Bruck Taddese ◽  
Alex C. Conner ◽  
David R. Poyner ◽  
Debbie L. Hay ◽  
...  
Keyword(s):  
G Protein ◽  
Calcitonin Gene Related Peptide ◽  
G Protein Coupled Receptors ◽  
Cgrp Receptor ◽  
Conserved Residues ◽  
Related Peptide ◽  
Class A ◽  
Calcitonin Gene ◽  
Class B ◽  
G Protein Coupled

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A–class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg 2.39 , His 2.43 and Glu 3.46 , which makes a polar lock with T 6.37 . These alignments and models provide useful tools for understanding class B GPCR function.

Modifications to the N-Terminus but Not the C-Terminus of Calcitonin Gene-Related Peptide(8-37) Produce Antagonists with Increased Affinity

2003 ◽  
Vol 46 (12) ◽  
pp. 2427-2435 ◽  
Author(s):  
D. David Smith ◽  
Shankar Saha ◽  
Guoyong Fang ◽  
Courtney Schaffert ◽  
David J. J. Waugh ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
C Terminus ◽  
Calcitonin Gene ◽  
N Terminus
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