scholarly journals Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Abimael González-Hernández ◽  
Bruno A. Marichal-Cancino ◽  
Jair Lozano-Cuenca ◽  
Jorge S. López-Canales ◽  
Enriqueta Muñoz-Islas ◽  
...  
Keyword(s):  
Vascular Tone ◽  
Transmembrane Protein ◽  
Therapeutic Implications ◽  
Cgrp Release ◽  
Receptor Component ◽  
Calcitonin Gene ◽  
Potent Vasodilator ◽  
Efferent Function ◽  
Sensory Fibers ◽  
G Protein Coupled

Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP andβ-CGRP), theα-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor). This receptor is an atypical G-protein coupled receptor (GPCR) composed of three functional proteins: (i) the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein), (ii) the activity-modifying protein type 1 (RAMP1), and (iii) a receptor component protein (RCP). Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia). The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.

Lack of Effect of the Adenosine A1 Receptor Agonist, GR79236, on Capsaicin-Induced CGRP Release in Anaesthetized Pigs

Cephalalgia ◽  
2005 ◽  
Vol 25 (11) ◽  
pp. 1082-1090 ◽  
Author(s):  
U Arulmani ◽  
JPC Heiligers ◽  
D Centurión ◽  
IM Garrelds ◽  
CM Villalón ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Sensory Nerves ◽  
Cgrp Release ◽  
Calcitonin Gene ◽  
Adenosine A1 ◽  
Potent Vasodilator ◽  
Haemodynamic Changes ◽  
A1 Receptor ◽  
The Difference ◽  
Prejunctional Inhibition

Migraine is a common neurological disorder that is associated with an increase in plasma calcitonin gene-related peptide (CGRP) levels. CGRP, a potent vasodilator released from the activated trigeminal sensory nerves, dilates intracranial blood vessels and transmits vascular nociception. Hence, inhibition of trigeminal CGRP release may prevent neurotransmission and, thereby, ameliorate migraine headache. Therefore, the present study in anaesthetized pigs investigates the effects of a selective adenosine A1 receptor agonist, GR79236 (3, 10 and 30 μg/kg, i.v.) on capsaicin-induced carotid haemodynamic changes and on plasma CGRP release. Intracarotid (i.c.) infusion of capsaicin (10 μg/kg/min, i.c.) increased the total carotid blood flow and conductance as well as carotid pulsations, but decreased the difference between arterial and jugular venous oxygen saturations. These responses to capsaicin were dose-dependently attenuated by GR79236. However, the increases in the plasma CGRP concentrations by capsaicin remained essentially unmodified after GR79236 treatment. The above results suggest that GR79236 may have an antimigraine potential due to its postjunctional effects (carotid vasoconstriction) rather than to prejunctional inhibition of trigeminal CGRP release.

Receptor component protein (RCP): a member of a multi-protein complex required for G-protein-coupled signal transduction

2002 ◽  
Vol 30 (4) ◽  
pp. 460-464 ◽  
Author(s):  
M. A. Prado ◽  
B. Evans-Bain ◽  
I. M. Dickerson
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Signal Transduction Pathway ◽  
Cgrp Receptor ◽  
Receptor Component ◽  
Calcitonin Gene ◽  
Cellular Signal ◽  
Cellular Signal Transduction Pathway ◽  
G Protein Coupled ◽  
Component Protein

The calcitonin-gene-related peptide (CGRP) receptor component protein (RCP) is a 148-amino-acid intracellular protein that is required for G-protein-coupled signal transduction at receptors for the neuropeptide CGRP. RCP works in conjunction with two other proteins to constitute a functional CGRP receptor: calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein 1 (RAMP1).CRLR has the stereotypical seven-transmembrane topology of a G-protein-coupled receptor; it requires RAMP1 for trafficking to the cell surface and for ligand specificity, and requires RCP for coupling to the cellular signal transduction pathway. We have made cell lines that expressed an antisense construct of RCP and determined that CGRP-mediated signal transduction was reduced, while CGRP binding was unaffected. Furthermore, signalling at two other endogenous G-protein-coupled receptors was unaffected, suggesting that RCP was specific for a limited subset of receptors.

scholarly journals Involvement of CGRP receptor RAMP1 in cluster headache: A Swedish case-control study

2019 ◽  
Vol 2 ◽  
pp. 251581631987988 ◽  
Author(s):  
Julia M Michalska ◽  
Caroline Ran ◽  
Carmen Fourier ◽  
Anna Steinberg ◽  
Christina Sjöstrand ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Mrna Expression ◽  
Quantitative Polymerase Chain Reaction ◽  
Active Phase ◽  
Nucleotide Polymorphisms ◽  
Cgrp Receptor ◽  
Receptor Component ◽  
Significant Difference ◽  
Potent Vasodilator ◽  
Primary Fibroblasts

Background: Increased levels of the potent vasodilator calcitonin gene-related peptide (CGRP) have been found in ipsilateral jugular vein blood during the active phase of cluster headache (CH) and this is hypothesized to cause distinctive vasodilation. The receptor activity-modifying protein 1 (RAMP1) is part of the CGRP receptor complex responsible for ligand binding and specificity and therefore constitutes a promising candidate gene for CH. The aim of this study was to investigate the possible genetic association of RAMP1 with CH in Sweden, with focus on two RAMP1 single nucleotide polymorphisms, rs3754701 and rs7590387, and quantify RAMP1 mRNA expression levels in biological tissue from CH patients and controls. Methods: rs3754701 and rs7590387 were genotyped by quantitative polymerase chain reaction (qPCR) in 542 CH patients and 585 control subjects. RAMP1 mRNA expression was determined by reverse transcription qPCR in tissue from 12 CH patients and 12 controls. Results: We identified a significant difference between the CH patient and control groups for rs3754701 ( p = 0.0088). In addition, RAMP1 mRNA expression was enhanced in primary fibroblasts from CH patients compared to controls ( p = 0.0073). Conclusion: The association between rs3754701 and CH and the enhanced RAMP1 mRNA expression in CH patients support the hypothesis that CGRP and its receptor component RAMP1 are involved in CH pathophysiology.

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.

Involvement of calcitonin gene-related peptide in control of human fetoplacental vascular tone

2004 ◽  
Vol 286 (1) ◽  
pp. H230-H239 ◽  
Author(s):  
Yuan-Lin Dong ◽  
Sujatha Vegiraju ◽  
Madhu Chauhan ◽  
Pandu R. R. Gangula ◽  
Gary D. V. Hankins ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Human Placenta ◽  
Vascular Tone ◽  
Umbilical Artery ◽  
Force Measurement ◽  
Isometric Force ◽  
Calcitonin Gene Related Peptide ◽  
Immunofluorescent Staining ◽  
Related Peptide ◽  
Calcitonin Gene

Calcitonin gene-related peptide (CGRP), one of the most potent endogenous vasodilators known, has been implicated in vascular adaptations and placental functions during pregnancy. The present study was designed to examine the existence of CGRP-A receptor components, the calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), in the human placenta and the vasoactivity of CGRP in the fetoplacental circulation. Immunofluorescent staining of the human placenta in term labor using polyclonal anti-CRLR and RAMP1 antibodies revealed that labeling specifically concentrated in the vascular endothelium and the underlying smooth muscle cells in the umbilical artery/vein, chorionic artery/vein, and stem villous vessels as well as in the trophoblast layer of the placental villi. In vitro isometric force measurement showed that CGRP dose dependently relaxes the umbilical artery/vein, chorionic artery/vein, and stem villous vessels. Furthermore, CGRP-induced relaxation of placental vessels are inhibited by a CGRP receptor antagonist (CGRP8–37), ATP-sensitive potassium (KATP) channel blocker (glybenclamide), and cAMP-dependent protein kinase A inhibitor (Rp-cAMPS) and partially inhibited by a nitric oxide inhibitor ( Nω-nitro-l-arginine methyl ester). We propose that CGRP may play a role in the control of human fetoplacental vascular tone, and the vascular dilations in response to CGRP may involve activation of KATP channels, cAMP, and a nitric oxide pathway.

scholarly journals Role of Calcitonin Gene Related Peptide (CGRP) in Migraine

2017 ◽  
Vol 33 (1) ◽  
pp. 39-43
Author(s):  
Md Ashraf Ali ◽  
Habibur Rahaman
Keyword(s):  
Family Relationships ◽  
Preventive Treatment ◽  
Primary Headache ◽  
Calcitonin Gene Related Peptide ◽  
Childhood And Adolescence ◽  
Protein Extravasation ◽  
Related Peptide ◽  
Plasma Protein Extravasation ◽  
Calcitonin Gene ◽  
Potent Vasodilator

Migraine is the second most primary headache. The prevalence of Migraine is 12% in the general population, including 18% in women and 6% in men. Migraine can start in childhood and adolescence and continue throughout lifespan. It is most prevalent among people in their 30s and 40s. Migraine is a debilitating hemicranial headache that is pulsating, aggravated by movement, nausea, vomiting and having sensitivity to light and sound, with or without aura. It can affect all aspects of life as work and school, parenting and family relationships and personal and leisure time. There are some theory regarding pathogenesis of migraine which includes cortical spreading depression, cortical spreading oligemia, activation of trigeminocervical complex leading to neuroinflammation & release of vasodialating neuropeptides which include calcitonin gene related peptide (CGRP), substance P, vasoactive intestinal polypeptide (VIP), nitric oxide (NO), and pituitary adenylate cyclase activating peptide (PACAP) & genetic factor. CGRP is a potent vasodilator and causes perivascular plasma protein extravasation and nociceptive pain. Newer medications target CGRP both for acute and preventive treatment of migraine. Bangladesh Journal of Neuroscience 2017; Vol.  33 (1): 39-43

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.

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