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The calcitonin gene-related peptide family pp 97–114Cite as

Genetic Regulation of CGRP and Its Actions

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Abstract

The calcitonin gene-related peptide (CGRP) gene is specifically expressed and regulated in a subset of cell types. Abnormal regulation of CGRP gene expression and/or sensitivity to CGRP actions may contribute to certain pathologies. In this chapter, we will summarize the current state of knowledge on the CGRP promoter and the use of a genetic strategy to sensitize mice to CGRP actions. The CGRP promoter is regulated by two distinct elements: a proximal cyclic AMP response element and a distal, regulated cell-specific enhancer. Both of these elements are activated by mitogen-activated protein kinase (MAPK) signaling pathways. MAPK can stimulate the CGRP promoter in response to proinflammatory cytokines. In addition, CGRP can directly activate these pathways to boost its own expression and potentially increase CGRP actions in a feedback loop. These pathways may contribute to the elevated CGRP levels in migraine and sepsis. Genetic enhancement of the CGRP receptor subunit, receptor activity-modifying protein-1 (RAMP1), increases CGRP actions in vascular smooth muscle and neurons. Potential implications of CGRP elevation and sensitization in migraine will be discussed.

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Abbreviations

3T3:

mouse fibroblast cell

C6:

rat glioma cell line

cAMP:

3′-5′-cyclic adenosine monophosphate

CGRP:

calcitonin gene-related peptide

CMV:

cytomegalovirus promoter

CLR:

calcitonin receptor-like receptor

CRE:

cAMP-response element

CREB:

cAMP-response element-binding protein

CT:

calcitonin

DRG:

dorsal root ganglia

GFP:

green fluorescent protein

hRAMP-1:

human receptor activity modifying protein-1

IL-1β:

interleukin 1 beta

IL-6:

interleukin 6

JNK:

c-Jun N-terminal kinase

LPS:

lipopolysaccharide

MAPK:

mitogen-activated protein kinase

MEK:

mitogen-activated protein kinase kinase

MTC:

medullary thyroid cell

NGF:

nerve growth factor

NO:

nitric oxide

PKA:

protein kinase A

PKC:

protein kinase C

RAMP-1:

receptor activity-modifying protein-1

RCP:

receptor component protein

RRE:

ras-responsive element

RREB:

ras-responsive element-binding protein

SCLC:

small cell lung carcinoma

TNF-α:

tumor necrosis factor alpha

USF:

upstream stimulatory factor

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Authors and Affiliations

  1. Molecular and Cellular Biology, University of Iowa, 5-432 BSB 51 Newton Road, Iowa City, 52242, IA, USA

    Ki-Youb Park

  2. Molecular Physiology and Biophysics, University of Iowa, 5-432 BSB 51 Newton Road, Iowa City, 52242, IA, USA

    Andrew F. Russo

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  1. Ki-Youb Park
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  2. Andrew F. Russo
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Correspondence to Andrew F. Russo .

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  1. School of Biological Sciences, University of Auckland, Symonds St. 9, Auckland , 1142, New Zealand

    Deborah L. Hay

  2. University of Auckland, Symonds Street 3A, Auckland, 1142, New Zealand

    Ian M. Dickerson

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Park, KY., Russo, A.F. (2010). Genetic Regulation of CGRP and Its Actions. In: Hay, D., Dickerson, I. (eds) The calcitonin gene-related peptide family. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2909-6_7

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