Interaction of calcitonin-gene-related peptide with its receptors

2002 ◽  
Vol 30 (4) ◽  
pp. 451-455 ◽  
Author(s):  
A. C. Conner ◽  
D. L. Hay ◽  
S. G. Howitt ◽  
K. Kilk ◽  
Ü. Langel ◽  
...  
Keyword(s):  
Direct Contact ◽  
Transmembrane Domain ◽  
Receptor Activation ◽  
Calcitonin Gene Related Peptide ◽  
Type Ii ◽  
Calcitonin Receptor ◽  
High Affinity ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
G Protein Coupled

The receptor for calcitonin-gene-related peptide (CGRP) is a heterodimer formed by calcitonin-receptor-like receptor (CRLR), a type II (family B) G-protein-coupled receptor, and receptor-activity-modifying protein 1 (RAMP1), a single-membrane-pass protein. It is likely that the first seven or so amino acids of CGRP (which form a disulphide-bonded loop) interact with the transmembrane domain of CRLR to cause receptor activation. The rest of the CGRP molecule falls into three domains. Residues 28–37 and 8–18 are normally required for high-affinity binding, while residues 19–27 form a hinge region. The 28–37 region is almost certainly in direct contact with the receptor; 8–18 may make additional receptor contacts or may stabilize an appropriate conformation of 28–37. It is likely that these regions of CGRP interact both with CRLR and with the extracellular domain of RAMP1.

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 Immunohistochemical Localization of Calcitonin Receptor–Like Receptor and Receptor Activity–Modifying Proteins in the Human Cerebral Vasculature

2002 ◽  
Vol 22 (5) ◽  
pp. 620-629 ◽  
Author(s):  
Kevin R. Oliver ◽  
Anna Wainwright ◽  
Lars Edvinsson ◽  
John D. Pickard ◽  
Raymond G. Hill
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Immunohistochemical Localization ◽  
Receptor Activity ◽  
Cell Surface Expression ◽  
Cerebral Vasculature ◽  
Calcitonin Receptor ◽  
Trigeminovascular System ◽  
High Affinity ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide and adrenomedullin belong to a structurally related neuropeptide family and are potent vasodilators expressed in the trigeminovascular system. The molecular identity of receptors for these proteins has only recently been elucidated. Central to functional binding of these neuropeptides is the G-protein–coupled receptor, the calcitonin receptor–like receptor (CRLR), whose cell surface expression and pharmacology is determined by coexpression of a receptor activity-modifying protein (RAMP). CRLR combined with RAMP1 binds calcitonin gene-related peptide with high affinity, whereas CRLR coexpression with RAMP2 or −3 confers high-affinity binding of adrenomedullin. The authors investigated the expression of these receptor components in human cerebral vasculature to further characterize neuropeptide receptor content and the potential functions of these receptors. Localization has been carried out using specific antisera raised against immunogenic peptide sequences that were subsequently applied using modern immunohistochemical techniques and confocal microscopy. The results are the first to show the presence of these receptor component proteins in human middle meningeal, middle cerebral, pial, and superficial temporal vessels, and confirm that both calcitonin gene-related peptide and adrenomedullin receptors may arise from the coassembly of RAMPs with CRLR in these vessel types. These novel data advance the understanding of the molecular function of the trigeminovascular system, its potential role in vascular headache disorders such as migraine, and may lead to possible ways in which future synthetic ligands may be applied to manage these disorders.

A New Calcitonin-Receptor-like Sequence in Rat Pulmonary Blood Vessels

1993 ◽  
Vol 85 (4) ◽  
pp. 385-388 ◽  
Author(s):  
F. Njuki ◽  
C. G. Nicholl ◽  
A. Howard ◽  
J. C. W. Mak ◽  
P. J. Barnes ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Vascular Tone ◽  
Islet Amyloid Polypeptide ◽  
Calcitonin Gene Related Peptide ◽  
Binding Activity ◽  
Calcitonin Receptor ◽  
Islet Amyloid ◽  
Related Peptide ◽  
Calcitonin Gene

1. Two rat clones have been isolated which are similar to known calcitonin-receptor sequences. One of these does not have the distribution expected of a calcitonin receptor. It is widely distributed, with extremely high levels of expression in the lung, where it is associated with the blood vessels. 2. This rat sequence may represent the receptor for calcitonin-gene-related peptide or islet amyloid polypeptide. Both have binding activity in the lung and are potent vasodilators. The gene represented by this sequence may therefore play an important role in the maintenance of vascular tone.

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 High‐dose phenylephrine increases meningeal blood flow through TRPV1 receptor activation and release of calcitonin gene‐related peptide

2019 ◽  
Vol 24 (2) ◽  
pp. 383-397 ◽  
Author(s):  
Mária Dux ◽  
Alexandru Babes ◽  
Jessica Manchen ◽  
Julika Sertel‐Nakajima ◽  
Birgit Vogler ◽  
...  
Keyword(s):  
Blood Flow ◽  
Receptor Activation ◽  
Calcitonin Gene Related Peptide ◽  
High Dose ◽  
Trpv1 Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Meningeal Blood Flow ◽  
Flow Through

Identification of High Affinity Calcitonin Gene?Related Peptide Receptors on a Murine Macrophage-like Cell Line

1990 ◽  
Vol 594 (1 Neuropeptides) ◽  
pp. 364-366 ◽  
Author(s):  
J. ABELLO ◽  
D. KAISERLIAN-NICOLAS ◽  
J. C. CUBER ◽  
J. P. REVILLARD ◽  
J. A. CHAYVIALLE
Keyword(s):  
Cell Line ◽  
Calcitonin Gene Related Peptide ◽  
Murine Macrophage ◽  
Peptide Receptors ◽  
High Affinity ◽  
Related Peptide ◽  
Calcitonin Gene
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