Sustained orexigenic effect of Agouti related protein may be not mediated by the melanocortin 4 receptor.
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.
Kim
Min Seon
MS
Department of Internal Medicine and Institute of Endocrinology, Nutrition and Metabolism, Medical Research Center, Seoul National University College of Medicine, 110-744, Seoul, South Korea.
Rossi
Michela
M
Abbott
Caroline R
CR
AlAhmed
Samaher H
SH
Smith
David M
DM
Bloom
Stephen R
SR
D054369:Agouti-Related Protein; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D019824:beta-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
C471568:11-Mrp-14-Nal-18-Cys-22-Asp-beta-MSH(11-22)NH2; C515198:AGRP protein, human; C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010456:Peptides, Cyclic; D011506:Proteins; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D019824:beta-MSH