Endothelin-1 in Human Skin: Immunolocalization, Receptor Binding, mRNA Expression, and Effects on Cutaneous Microvascular Endothelial Cells

Endothelin-1 in Human Skin: Immunolocalization, Receptor Binding, mRNA Expression, and Effects on Cutaneous Microvascular Endothelial Cells

Endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been implicated in the maintenance of systemic and peripheral vascular tone. We have therefore sought direct evidence of a role for FT-1 in the regulation of blood flow and vascular tone in the human cutaneous microvasculature. Immunostainin...

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Bibliographic Details
Published in:Journal of investigative dermatology Vol. 97; no. 4; pp. 618 - 623
Main Authors: Bull, Helen A., Bunker, Christopher B., Terenghi, Georgio, Springall, David R., Zhao, Yidan, Polak, Julia M., Dowd, Pauline M.
Format: Journal Article
Language:English
Published: Danvers, MA Elsevier Inc 01-10-1991
Nature Publishing
Subjects:
Biological and medical sciences
Calcium - physiology
Cells, Cultured
Cyclic AMP - metabolism
Dinoprostone - metabolism
Endothelins - analysis
Endothelins - metabolism
Endothelins - pharmacology
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
General aspects
Humans
Immunohematology
Immunohistochemistry
Receptors, Cell Surface - metabolism
Receptors, Endothelin
RNA, Messenger - analysis
Skin - chemistry
Human
Cell culture
Molecular hybridization
Endothelial cell
Messenger RNA
Immunocytochemistry
In situ
Vasoconstrictor agent
Endothelin 1
Skin
Localization
Blood flow
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Summary:Endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been implicated in the maintenance of systemic and peripheral vascular tone. We have therefore sought direct evidence of a role for FT-1 in the regulation of blood flow and vascular tone in the human cutaneous microvasculature. Immunostaining for ET-1 was observed in all cutaneous blood vessels of normal human skin including the capillaries of the dermal papillae. Autoradiography showed specific binding of 125I-ET-1 over capillaries and larger blood vessels as well as hair follicles and sweat glands. In situ hybridization with a 32P-labeled RNA probe for ET-1 demonstrated mRNA for ET-1 in cultured human dermal microvascular endothelial cells (HDMEC). In HDMEC, basal release of PGE2 was significantly attenuated by FT-1 (100pM -100 nM) (p < 0.05, n = 7) with maximum inhibition in cells incubated with 10nM ET-1. ET-1 also increased intracellular cAMP in a dose-dependent manner with a significant increase in HDMEC incubated with 100nM ET-1 (p < 0.05, n = 4). In HDMIEC incubated with 100nM ET-1, inhibition of PGE2 release was unaffected by the dihydropyridine Ca++ channel antagonist nifedipine or the extracellular Ca++ chelator EGTA, whereas the intracellular Ca++ chelator TMB-8 partially blocked the action of ET-1. In contrast, cAMP accumulation was significantly attenuated by EGTA (p < 0.05, n = 4), nifedipine (p < 0.05, n = 4), and TMB-8 (p < 0.05, n = 4), indicating that the endothelial cell responses to ET-1 are complex and appear to involve both. Ca++ sensitive and -insensitive pathways. These results provide evidence of an autocrine/paracrine role for ETA in the human cutaneous microvasculature.
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ISSN:0022-202X
1523-1747
DOI:10.1111/1523-1747.ep12483000