Abstract
HEK 293 cells stably expressing human melanocortin-3 receptor (MC3R) were exposed to melanocortin receptor agonist, NDP-MSH (10(-)(10)-10(-)(6) M). ERK1/2 was phosphorylated in a dose-dependent manner with an EC(50) of 3.3+/-1.5 x 10(-)(9) M, similar to the IC(50) of NDP-MSH binding to the MC3R. ERK1/2 phosphorylation was blocked by the melanocortin receptor antagonists SHU9119. NDP-MSH-induced ERK1/2 phosphorylation was sensitive to pertussis toxin and the PI3K inhibitor, wortmannin. Rp-cAMPS, BAPTA-AM and Myr-PKC did not inhibit the NDP-MSH-induced ERK1/2 phosphorylation. NDP-MSH stimulated cellular proliferation in a dose-dependent manner with a similar EC(50) to ERK1/2 phosphorylation, 2.1+/-0.6 x 10(-)(9) M. Cellular proliferation was blocked by AGRP (86-132) and by the MEK inhibitor, PD98059. The NDP-MSH did not inhibit serum deprivation-induced apoptosis. MC3R activation induces ERK1/2 phosphorylation via PI3K and this pathway is involved in cellular proliferation in HEK cells expressing MC3R.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Agouti-Related Protein
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Apoptosis / drug effects
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Blotting, Western
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Cell Line
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Flavonoids / pharmacology
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Humans
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Mitogen-Activated Protein Kinases / metabolism*
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Peptide Fragments / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphorylation / drug effects
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Receptor, Melanocortin, Type 3 / antagonists & inhibitors
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Receptor, Melanocortin, Type 3 / physiology*
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alpha-MSH / analogs & derivatives
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alpha-MSH / pharmacology
Substances
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Agouti-Related Protein
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Flavonoids
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Peptide Fragments
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Receptor, Melanocortin, Type 3
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agouti-related protein (86-132), human
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alpha-MSH
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MSH, 4-Nle-7-Phe-alpha-
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Phosphatidylinositol 3-Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one