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CGRP: a Multifunctional Neuropeptide

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

It has been just over 20 years since the neuropeptide calcitonin gene‐related peptide (CGRP) was unexpectedly discovered embedded within the calcitonin gene. Since then CGRP has emerged as a key regulator of multiple physiological and pathological functions. CGRP is expressed in a subset of neurons in the central and peripheral nervous system that innervate every major organ system. Within this context, CGRP is a multifunctional peptide that is a major modulator of the cardiovascular system and a key player in neurogenic inflammatory pain. Since the discovery of CGRP, a repertoire of related peptides have been identified. The expression patterns and activities of these family members are discussed briefly. We will focus on how CGRP gene transcription is controlled by extracellular signals that target the cell‐specific and cAMP‐regulated enhancers. An emphasis of the chapter will be the unusual mechanism by which the CGRP receptor requires the G‐protein‐coupled calcitonin‐like receptor (CLR), receptor activity modifying protein‐1 (RAMP1), and receptor component protein (RCP). We will then address the physiological activities of CGRP in the cardiovascular and smooth muscle, skeletal muscle, and cochlear systems. Finally, we will discuss two pathologies that involve CGRP in the trigeminovascular system: migraine and subarachnoid hemorrhage (SAH). The efficacy of a CGRP receptor antagonist has now established the importance of elevated CGRP in migraine. In contrast, the lack of CGRP may contribute to fatal vasospasms in SAH. Thus, the continuing development of pharmacological and genetic approaches for modulating CGRP expression and activity holds exciting promise for future therapeutic strategies.

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Abbreviations

ABR:

auditory brainstem response

ACh:

acetylcholine

AChE:

acetylcholinesterase

AChR:

acetylcholine receptor

AM:

adrenomedullin

bHLH‐Zip:

basic HLH‐leucine zipper

cAMP:

cyclic adenosine monophosphate

CGRP:

calcitonin gene‐related peptide

CLR:

calcitonin‐like receptor

CRSP:

calcitonin receptor‐stimulating peptide

CRE:

cAMP response element

CREB:

cAMP response element binding protein

CT:

calcitonin

CTR:

calcitonin receptor

DAG:

diacylglycerol

DPOAE:

distortion product otoacoustic emissions

DRG:

dorsal root ganglia

Fox:

forkhead

HLH:

helix–loop–helix

5‐HT1 :

5‐hydroxytryptamine 1

IP3:

inositol‐1,4,5‐trisphosphate

MAPK:

mitogen‐activated protein kinase

MASH‐1:

mammalian achaete‐scute homolog‐1

MKP‐1:

MAP kinase phosphatase‐1

PDGF:

platelet‐derived growth factor

PIP2 :

phosphatidylinositol‐4,5‐bisphosphate

PKA:

protein kinase A

PKC:

protein kinase C

RAMP:

receptor activity modifying protein

RCP:

receptor component protein

SAH:

subarachnoid hemorrhage

USF:

upstream stimulatory factor

VSMC:

vascular smooth muscle cell

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Acknowledgments

The authors are supported by grants from NIH (DE016511, HL14388, DK52328).

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  1. A. F. Russo
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  2. I. M. Dickerson
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, Newyork, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurology (Division of Neurochemistry and Neurobiology), University of Iowa College of Medicine and Veterans Administration Medical Center, 52242, lowa, lowa, USA

    Ramon Lim

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Russo, A.F., Dickerson, I.M. (2006). CGRP: a Multifunctional Neuropeptide. In: Lajtha, A., Lim, R. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30381-9_19

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