Abstract
Intracerebroventricular (ICV) injection of Agouti related protein (AgRP), an endogenous melanocortin 3 and 4 receptor (MC3/4-R) antagonist, produces a prolonged increase in food intake. To clarify the roles of the MC3-R and MC4-R in AgRP-induced hyperphagia, the feeding effect of AgRP (83-132) was compared with that of the selective MC4-R antagonist, JKC-363 (cyclic [Mpr11, D-Nal14, Cys18, Asp22-NH2]-beta-MSH11-22). Single ICV administration of AgRP (83-132) increased food intake for 48 h whilst ICV JKC-363 increased food intake for 8h. An increase in body weight at 24 and 48 h was observed following AgRP (83-132) but not JKC-363 treatment. These data suggest that the sustained orexigenic action of AgRP (83-132) may not be through MC4-R antagonism.
MeSH terms
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Agouti-Related Protein
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Animals
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Appetite / drug effects*
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Body Weight / drug effects*
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Cell Line
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Dose-Response Relationship, Drug
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Feeding Behavior
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Humans
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Hypothalamus / metabolism
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Intercellular Signaling Peptides and Proteins
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Male
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Peptides / chemistry
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Peptides, Cyclic / pharmacology
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Proteins / pharmacology*
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Rats
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Rats, Wistar
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Receptor, Melanocortin, Type 3
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Receptor, Melanocortin, Type 4
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Receptors, Corticotropin / antagonists & inhibitors
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Receptors, Corticotropin / metabolism*
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Time Factors
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beta-MSH / analogs & derivatives
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beta-MSH / pharmacology
Substances
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11-Mrp-14-Nal-18-Cys-22-Asp-beta-MSH(11-22)NH2
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AGRP protein, human
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AGRP protein, rat
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Agouti-Related Protein
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Intercellular Signaling Peptides and Proteins
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Peptides
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Peptides, Cyclic
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Proteins
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Receptor, Melanocortin, Type 3
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Receptor, Melanocortin, Type 4
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Receptors, Corticotropin
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beta-MSH