The Transmembrane Domain of Receptor-Activity-Modifying Protein 1 Is Essential for the Functional Expression of a Calcitonin Gene-Related Peptide Receptor†

Biochemistry ◽  
2002 ◽  
Vol 41 (38) ◽  
pp. 11398-11404 ◽  
Author(s):  
Sarah Steiner ◽  
Roman Muff ◽  
Remo Gujer ◽  
Jan A. Fischer ◽  
Walter Born
Keyword(s):  
Transmembrane Domain ◽  
Functional Expression ◽  
Calcitonin Gene Related Peptide ◽  
Receptor Activity ◽  
Peptide Receptor ◽  
Related Peptide ◽  
Calcitonin Gene

scholarly journals Overview of Calcitonin Gene-Related Peptide and Its Receptor

2001 ◽  
Vol 1 ◽  
pp. 1-1 ◽  
Author(s):  
Nambi Aiyar
Keyword(s):  
Transmembrane Domain ◽  
Biological Activities ◽  
Cardiovascular Effects ◽  
Functional Expression ◽  
Calcitonin Gene Related Peptide ◽  
Structural Modifications ◽  
Amino Acid Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
C And N

Calcitonin Gene-Related Peptide (CGRP), a 37 amino acid peptide identified as the alternately spliced gene product of calcitonin gene, is a sensory neuropeptide with potent cardiovascular effects. CGRP is distributed throughout the central and peripheral nervous systems and possesses diverse biological actions. CGRP has been suggested to play a role in diseases such as migraine, diabetes, pain, and inflammation. Two forms of CGRP (alpha and beta) that differ in three amino acids have been identified and are encoded by different genes. Based on the differential biological activities of various CGRP analogs, the CGRP receptors have been classified into CGRP1 and CGRP2. Structure-activity studies of CGRP analogs showed that the C- and N-terminal regions of the peptide interact independently with their receptors. While C-terminal peptide, CGRP (8-37) behaves as a CGRP1 receptor antagonist, N-terminal peptide CGRP (1-12) behaves as a weak agonist. Structural modifications of CGRP(28-37) have yielded micromolar to nanomolar affinity ligands. CGRP receptor belongs to the calcitonin receptor like receptor (CRLR) family of G-protein-coupled receptors and has been shown to require a single transmembrane domain protein called receptor activity modifying protein-1 (RAMP1) for its functional expression as well as activity. Human, rat, and porcine CRLRs have been cloned and characterized. Currently, the major focus is on the identification of potent and specific nonpeptide antagonists for this receptor in order to understand the physiological and pathophysiological role of this peptide.

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.

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