Abstract
The melanocortin 4 receptor (MC4-R) is a Galpha s-coupled receptor known to increase cAMP production following agonist stimulation. We demonstrate that the mitogen-activated protein kinases p42 (ERK2) and p44 (ERK1) are also activated by MC4-R following treatment with the MC4-R agonist NDP-alpha-MSH in stably transfected CHO-K1 cells. This time- and dose-dependent response is abolished by the MC4-R antagonist SHU-9119. p42/p44 MAPK activation is blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 but not by the protein kinase A (PKA) inhibitor Rp-cAMPS, indicating that that signal activating the p42/p44 MAPK pathway is conveyed through inositol triphosphate.
MeSH terms
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Androstadienes / pharmacology
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Animals
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CHO Cells
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Cells, Cultured
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Chromones / pharmacology
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Cricetinae
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / pharmacology
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Cyclic AMP-Dependent Protein Kinases / pharmacology
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Melanocyte-Stimulating Hormones / pharmacology
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Mitogen-Activated Protein Kinase 3 / metabolism*
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Morpholines / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism*
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Protein Kinase Inhibitors / pharmacology
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Receptor, Melanocortin, Type 4 / antagonists & inhibitors*
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Receptor, Melanocortin, Type 4 / metabolism
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Signal Transduction
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Wortmannin
Substances
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Androstadienes
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Chromones
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Enzyme Inhibitors
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Morpholines
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Protein Kinase Inhibitors
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Receptor, Melanocortin, Type 4
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SHU 9119
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Melanocyte-Stimulating Hormones
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Cyclic AMP
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Phosphatidylinositol 3-Kinases
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 3
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Wortmannin