Calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and calcitonin gene-related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: Differences between peripheral and central CGRP receptor distribution

2008 ◽  
Vol 507 (3) ◽  
pp. 1277-1299 ◽  
Author(s):  
Jochen K. Lennerz ◽  
Victor Rühle ◽  
Eugene P. Ceppa ◽  
Winfried L. Neuhuber ◽  
Nigel W. Bunnett ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Receptor Activity ◽  
Calcitonin Receptor ◽  
Cgrp Receptor ◽  
Trigeminovascular System ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Receptor Distribution

scholarly journals CGRP Receptor Family and Accessory Protein Localization: Implications for Predicted Function

2001 ◽  
Vol 1 ◽  
pp. 10-10
Author(s):  
K.R. Oliver
Keyword(s):  
Protein Localization ◽  
Calcitonin Gene Related Peptide ◽  
Receptor Activity ◽  
Calcitonin Receptor ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Cellular Expression ◽  
Receptor Component ◽  
Calcitonin Gene ◽  
Receptor Activity Modifying Proteins

Calcitonin gene-related peptide (CGRP), adrenomedullin, amylin, and calcitonin are functionally related neuropeptides. Certain of these peptides mediate their action through receptors which have common components, such as the receptor activity modifying proteins (RAMPs) and CGRP-receptor component protein, as well as possibly through other distinct receptors. Specifically, the molecular pharmacology of CGRP and adrenomedullin is determined by coexpression of one of three receptor activity-modifying proteins (RAMPs) with calcitonin receptor-like receptor (CRLR). Additionally, through formation of another hetero-oligomer, RAMPs also govern the pharmacology of the calcitonin receptor, which in association with RAMP1 or RAMP3, binds amylin with high affinity. We have used multiple approaches to discern the regional and cellular expression of these various receptor components and binding sites for the above neuropeptides in multiple species and in different tissues. Techniques applied include in situ hybridization, immunohistochemistry and radioligand autoradiography. These data allow further understanding of both the complexity of receptor-receptor component and receptor-ligand interactions in vivo. Interestingly, these localization data suggest that RAMPs may interact with receptors additional to those already identified for the CGRP family and may be involved in binding innate neuropeptides or other neurotransmitters which are not members of the calcitonin gene-related peptide fam

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.

Distribution of CGRP and CGRP receptor components in the rat brain

Cephalalgia ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 342-353 ◽  
Author(s):  
Karin Warfvinge ◽  
Lars Edvinsson
Keyword(s):  
Rat Brain ◽  
Calcitonin Gene Related Peptide ◽  
Receptor Activity ◽  
Calcitonin Receptor ◽  
Thalamic Nuclei ◽  
Peptide Receptor ◽  
Brain Functions ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Neuronal Processes

Background Calcitonin gene-related peptide and its receptor, consisting of receptor activity-modifying protein 1 and calcitonin receptor-like receptor, are of considerable interest because of the role they play in migraine and recently developed migraine therapies. Methods To better understand the function of this neuropeptide, we used immunohistochemistry to determine a detailed distribution of calcitonin gene-related peptide, receptor activity-modifying protein 1 and calcitonin receptor-like receptor in the rat brain in a region of 0.5–1.5 mm lateral to the midline. We found calcitonin gene-related peptide immunoreactivity in most of the neurons of the cerebral cortex, hippocampus, cerebellum, thalamic nuclei, hypothalamic nuclei and brainstem nuclei. In contrast, receptor activity-modifying protein 1 and calcitonin receptor-like receptor immunoreactivity were found almost exclusively in the neuronal processes in the investigated regions. Conclusion Overall, the degree of expression of calcitonin gene-related peptide and calcitonin gene-related peptide receptor components in the central nervous system is astonishingly complex and suggestive of many different brain functions, including a possible role in migraine. However, currently, the presence of calcitonin gene-related peptide and the nature of its receptors throughout the brain is an enigma yet to be solved.

Molecular studies of CGRP and the CGRP family of peptides in the central nervous system

Cephalalgia ◽  
2018 ◽  
Vol 39 (3) ◽  
pp. 403-419 ◽  
Author(s):  
Erica R Hendrikse ◽  
Rebekah L Bower ◽  
Debbie L Hay ◽  
Christopher S Walker
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Calcitonin Gene Related Peptide ◽  
Receptor Activity ◽  
Peptide Sequence ◽  
Calcitonin Receptor ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
The Central Nervous System ◽  
Receptor Biology

Background Calcitonin gene-related peptide is an important target for migraine and other painful neurovascular conditions. Understanding the normal biological functions of calcitonin gene-related peptide is critical to understand the mechanisms of calcitonin gene-related peptide-blocking therapies as well as engineering improvements to these medications. Calcitonin gene-related peptide is closely related to other peptides in the calcitonin gene-related peptide family of peptides, including amylin. Relatedness in peptide sequence and in receptor biology makes it difficult to tease apart the contributions that each peptide and receptor makes to physiological processes and to disorders. Summary The focus of this review is the expression of calcitonin gene-related peptide, related peptides and their receptors in the central nervous system. Calcitonin gene-related peptide is expressed throughout the nervous system, whereas amylin and adrenomedullin have only limited expression at discrete sites in the brain. The components of two receptors that respond to calcitonin gene-related peptide, the calcitonin gene-related peptide receptor (calcitonin receptor-like receptor with receptor activity-modifying protein 1) and the AMY1 receptor (calcitonin receptor with receptor activity-modifying protein 1), are expressed throughout the nervous system. Understanding expression of the peptides and their receptors lays the foundation for more deeply understanding their physiology, pathophysiology and therapeutic use.

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