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Vascular Actions of CGRP and Adrenomedullin: Mechanisms and Potential Contribution to Inflammation in the Cutaneous Microvasculature

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The calcitonin gene-related peptide family

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Abstract

Calcitonin gene-related peptide (CGRP) has a well known hypotensive effect on blood pressure primarily due to dilatation of small resistance vessels. This microvascular vasodilator effect can also lead to potentiation of inflammatory oedema formation and cell accumulation in the cutaneous microvasculature when applied or released locally. Moreover, an involvement of CGRP in hyperalgesia accompanying the inflammatory processes has been confirmed. Adrenomedullin (AM) is a member of calcitonin peptide family first isolated from pheochromocytoma cells. It is primarily produced by non-neural cell types. AM acts on CGRP receptors and also activates AM1 receptors, which CGRP does not. Both are G protein-linked receptors consisting of the same calcitonin receptor-like receptor in association with a different receptor activity modifying proteins. In this chapter we compare the actions of AM and CGRP on the microcirculation, on inflammatory oedema formation/cell accumulation and hyperalgesia.

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Abbreviations

Akt:

protein kinase B

AM:

adrenomedullin

CGRP:

calcitonin gene-related peptide

CL:

calcitonin receptor-like receptor

DRG:

dorsal root ganglion

GDNF:

glia-derived neurotrophic factor

GSK3β:

glycogen synthase kinase 3 beta

IB4:

isolectin B4

IFNγ:

interferon gamma

IL-1β:

interleukin 1 beta

IL-6:

interleukin 6

LI:

lamina I of the dorsal horn

LIIi:

inner lamina II of the dorsal horn

LIIo:

outer lamina II of the dorsal horn

LPS:

lipopolysaccharide

MPO:

myeloperoxidase

NGF:

nerve growth factor

NK1:

neurokinin 1 receptor

NKA:

neurokinin A

NKB:

neurokinin B

NO:

nitric oxide

PI3K:

phosphoinositide 3-kinase

RAMP:

receptor activity modifying peptide

SP:

substance P

TNFα:

tumor necrosis factor alpha

TRPV1:

transient receptor potential vanilloid 1

VIP:

vasoactive intestinal peptide

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Acknowledgments

We thank the British Heart Foundation and the British Biotechnology Science Research Council (BBSRC) for funding. LL is supported by an IMB capacity building award.

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Authors and Affiliations

  1. Cardiovascular Division, King’s College London, Franklin-Wilkins Building, Waterloo Campus, 150 Stamford Street, London, SE1 9NH, UK

    Gabor Pozsgai, Lihuan Liang & Susan D. Brain

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  1. Gabor Pozsgai
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  2. Lihuan Liang
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  3. Susan D. Brain
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Correspondence to Susan D. Brain .

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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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Pozsgai, G., Liang, L., Brain, S.D. (2010). Vascular Actions of CGRP and Adrenomedullin: Mechanisms and Potential Contribution to Inflammation in the Cutaneous Microvasculature. In: Hay, D., Dickerson, I. (eds) The calcitonin gene-related peptide family. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2909-6_8

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