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The vasorelaxant effect of adrenomedullin, proadrenomedullin N-terminal 20 peptide and amylin in human skin

Hasbak, Philip ; Eskesen, Karen ; Lind, Henrik ; Holst, Jan LU and Edvinsson, Lars LU (2006) In Basic & Clinical Pharmacology & Toxicology 99(2). p.162-167
Abstract
In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenenous neuropeptides calcitonin gene-related peptide (CGRP) and substance P and to examine the mRNA expression of calcitonin receptor-like receptor (CL-R) and receptor-activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection of the peptides. The mRNA expression was assessed by real-time reverse transcriptase polymerase chain reaction (real-time PCR). CGRP, adrenomedullin... (More)
In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenenous neuropeptides calcitonin gene-related peptide (CGRP) and substance P and to examine the mRNA expression of calcitonin receptor-like receptor (CL-R) and receptor-activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection of the peptides. The mRNA expression was assessed by real-time reverse transcriptase polymerase chain reaction (real-time PCR). CGRP, adrenomedullin and amylin induced concentration-dependent, long-lasting increases in skin blood flow. The response to PAMP was shorter in duration appearing similar to the transient response induced by substance P. PAMP (10(-6)-10(-5)M) caused distinct itch sensation and local erythema. This effect could be abolished when combining the histamine H-1-receptor antagonist mepyramin and PAMP. Real-time PCR data showed a higher level of mRNA for RAMP2 than CL-R, RAMP1 and RAMP3 in the tissue. Though the PCR data demonstrated the presence of mRNA for both CGRP1 and adrenomedullin receptors the rank order of potency (CGRP > adrenomedullin > amylin) for the blood flow increase indicated vasodilatation for these peptides was induced by activation of CGRP1 receptors. Intradermal injection of CGRP, adrenomedullin and amylin induces long lasting dilatation of human skin vasculature by activation of CGRP1 receptors. PAMP induces transient vasodilatation. PAMP but not CGRP, adrenomedullin and amylin causes itch sensation and local erythema. The transient effect on vasodilatation as response to PAMP is discussed. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Basic & Clinical Pharmacology & Toxicology
volume
99
issue
2
pages
162 - 167
publisher
Wiley-Blackwell
external identifiers
  • wos:000239637100012
  • pmid:16918718
  • scopus:33747037205
ISSN
1742-7843
DOI
10.1111/j.1742-7843.2006.pto_465.x
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200), Medicine (Lund) (013230025)
id
164980e2-fd2c-4d11-bb7e-68825a367429 (old id 398521)
date added to LUP
2016-04-01 12:37:08
date last changed
2020-11-03 04:55:22
@article{164980e2-fd2c-4d11-bb7e-68825a367429,
  abstract     = {In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenenous neuropeptides calcitonin gene-related peptide (CGRP) and substance P and to examine the mRNA expression of calcitonin receptor-like receptor (CL-R) and receptor-activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection of the peptides. The mRNA expression was assessed by real-time reverse transcriptase polymerase chain reaction (real-time PCR). CGRP, adrenomedullin and amylin induced concentration-dependent, long-lasting increases in skin blood flow. The response to PAMP was shorter in duration appearing similar to the transient response induced by substance P. PAMP (10(-6)-10(-5)M) caused distinct itch sensation and local erythema. This effect could be abolished when combining the histamine H-1-receptor antagonist mepyramin and PAMP. Real-time PCR data showed a higher level of mRNA for RAMP2 than CL-R, RAMP1 and RAMP3 in the tissue. Though the PCR data demonstrated the presence of mRNA for both CGRP1 and adrenomedullin receptors the rank order of potency (CGRP > adrenomedullin > amylin) for the blood flow increase indicated vasodilatation for these peptides was induced by activation of CGRP1 receptors. Intradermal injection of CGRP, adrenomedullin and amylin induces long lasting dilatation of human skin vasculature by activation of CGRP1 receptors. PAMP induces transient vasodilatation. PAMP but not CGRP, adrenomedullin and amylin causes itch sensation and local erythema. The transient effect on vasodilatation as response to PAMP is discussed.},
  author       = {Hasbak, Philip and Eskesen, Karen and Lind, Henrik and Holst, Jan and Edvinsson, Lars},
  issn         = {1742-7843},
  language     = {eng},
  number       = {2},
  pages        = {162--167},
  publisher    = {Wiley-Blackwell},
  series       = {Basic & Clinical Pharmacology & Toxicology},
  title        = {The vasorelaxant effect of adrenomedullin, proadrenomedullin N-terminal 20 peptide and amylin in human skin},
  url          = {http://dx.doi.org/10.1111/j.1742-7843.2006.pto_465.x},
  doi          = {10.1111/j.1742-7843.2006.pto_465.x},
  volume       = {99},
  year         = {2006},
}