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CGRP Receptor Signalling Pathways

  • Graeme S. CottrellEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 255)

Abstract

Calcitonin gene-related peptide (CGRP) is a promiscuous peptide, similar to many other members of the calcitonin family of peptides. The potential of CGRP to act on many different receptors with differing affinities and efficacies makes deciphering the signalling from the CGRP receptor a challenging task for researchers.

Although it is not a typical G protein-coupled receptor (GPCR), in that it is composed not just of a GPCR, the CGRP receptor activates many of the same signalling pathways common for other GPCRs. This includes the family of G proteins and a variety of protein kinases and transcription factors. It is now also clear that in addition to the initiation of cell-surface signalling, GPCRs, including the CGRP receptor, also activate distinct signalling pathways as the receptor is trafficking along the endocytic conduit.

Given CGRP’s characteristic of activating multiple GPCRs, we will first consider the complex of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) as the CGRP receptor. We will discuss the discovery of the CGRP receptor components, the molecular mechanisms controlling its internalization and post-endocytic trafficking (recycling and degradation) and the diverse signalling cascades that are elicited by this receptor in model cell lines. We will then discuss CGRP-mediated signalling pathways in primary cells pertinent to migraine including neurons, glial cells and vascular smooth muscle cells.

Investigation of all the CGRP- and CGRP receptor-mediated signalling cascades is vital if we are to fully understand CGRP’s role in migraine and will no doubt unearth new targets for the treatment of migraine and other CGRP-driven diseases.

Keywords

Calcitonin gene-related peptide Calcitonin receptor-like receptor G protein Protein kinase Receptor activity-modifying protein Signalling Trafficking 

Abbreviations

ATP

Adenosine triphosphate

cAMP

Cyclic adenosine monophosphate

CGRP

Calcitonin gene-related peptide

CLR

Calcitonin receptor-like receptor

ECE1

Endothelin-converting enzyme 1

ERK

Extracellular-regulated protein kinase

ETA

Endothelin A receptor

GPCR

G protein-coupled receptor

IL

Interleukin

JNK

c-Jun N-terminal kinase

PKA

Protein kinase A

PKC

Protein kinase C

NO

Nitric oxide

NOS

Nitric oxide synthase

RAMP

Receptor activity-modifying protein

RCP

Receptor component protein

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of ReadingReadingUK

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