The role of the melanocortin 3 receptor in mediating the effects of gamma-MSH peptides on the adrenal.
The pro-opiomelanocortin (POMC)-derived peptides, pro-gamma-MSH (16K fragment), and Lys-gamma3-MSH, have been shown to potentiate the steroidogenic action of corticotrophin (ACTH) on the adrenal cortex. Using a continuously perfused adrenal cell column system, we have tested the hypothesis that gamma-MSH peptides exert their effect through the Melanocortin 3 Receptor (MC3-R), since this is the only known receptor to have high affinity for gamma-MSH peptides and has been suggested to be expressed in the rat adrenal. To investigate this hypothesis we tested whether the MC3-R agonist MTII and antagonist SHU9119 could mimic or block the actions of pro-gamma-MSH. We found that MTII could not mimic, and SHU9119 could not block pro-gamma-MSH mediated potentiation of ACTH-induced steroidogenesis. These results suggest that the MC3-R is not involved in mediating the potentiation effect, adding further evidence to the argument that another melanocortin receptor exists.
Harmer
Stephen C
SC
School of Animal and Microbial Sciences, The University of Reading, Reading, Berkshire, UK.
Bicknell
Andrew B
AB
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D005260:Female; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044104:Receptor, Melanocortin, Type 3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013256:Steroids / Q000096:biosynthesis*; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology; D019825:gamma-MSH / Q000494:pharmacology*
D010446:Peptide Fragments; D044104:Receptor, Melanocortin, Type 3; D013256:Steroids; C105974:acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide; D019825:gamma-MSH; C103272:SHU 9119; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones