Research article summary (published 30 Jul 2006):

Adrenomedullin increases the expression of calcitonin-like receptor and receptor activity modifying protein 2 mRNA in human microvascular endothelial cells.

Full Abstract

Adrenomedullin (AM) is a multifunctional peptide hormone, which plays a significant role in vasodilation and angiogenesis, implicating it in hypertension as well as in carcinogenesis. AM exerts its effects via the calcitonin receptor-like receptor (CRLR, now known as CL) complexed with either receptor activity modifying protein (RAMP) 2 or 3. We have investigated the effect of AM on immortalized human microvascular endothelial cells 1, since endothelial cells are a major source as well as a target of AM actions in vivo. Cells treated with AM showed elevated cAMP in a time (5-45 min)-dependent and dose (10(-6)-10(-14) M)-dependent manner. Pre-treatment with the AM receptor antagonist AM(22-52) partially suppressed the AM-induced increase in cAMP levels. An increase in extracellular signal-regulated kinase 1/2 phosphorylation was observed after 5 min of treatment with 10(-8) M AM. This phosphorylation was specific, since we were able to block the AM-induced effect with 1 microM U0126, a specific mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor. Using real-time PCR, we were able to show for the first time that AM upregulates peptide and mRNA expression of vascular endothelial growth factor (VEGF). However, AM treatment of cells did not result in increased cell proliferation. Instead, we observed that AM and VEGF induced cell migration, which could be inhibited by the AM(22-52) and anti-VEGF antibody respectively. AM also significantly elevated mRNA levels of CL (after 2 and 24 h treatment) and RAMP2 (after 1 and 24 h treatment). The upregulation of the AM receptor at two time points reflects possibly different cellular responses to short- and long-term exposure to AM.

Author information

Author/s: Schwarz, Nele (N); Renshaw, Derek (D); Kapas, Supriya (S); Hinson, Joy P (JP);

Affiliation: Centre of Molecular Endocrinology, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary University, London, UK.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of endocrinology (J Endocrinol), published in England. (Language: eng)

Reference: 2006-Aug; vol 190 (issue 2) : pp 505-14

Dates: Created 2006/08/10; Completed 2006/11/07; Revised 2006/11/15;

PMID: 16899583, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adrenomedullin Analysis of Variance Blotting, Western - methods Cell Line Cell Movement - drug effects Cell Proliferation - drug effects Cyclic AMP - analysis Endothelial Cells - metabolism Endothelium, Vascular - metabolism Humans

Humans Intracellular Signaling Peptides and Proteins - genetics; metabolism Membrane Proteins - genetics; metabolism Microcirculation Peptides - pharmacology RNA, Messenger - analysis; metabolism Receptors, Calcitonin - genetics; metabolism Reverse Transcriptase Polymerase Chain Reaction Stimulation, Chemical Vascular Endothelial Growth Factor A - analysis

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: CLR protein, human (0) ; Intracellular Signaling Peptides and Proteins (0) ; Membrane Proteins (0) ; Peptides (0) ; RNA, Messenger (0) ; Receptors, Calcitonin (0) ; Vascular Endothelial Growth Factor A (0) ; receptor-activity-modifying protein (0) ; Adrenomedullin (148498-78-6) ; Cyclic AMP (60-92-4)

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