Asp10 in Lys-gamma2-MSH determines selective activation of the melanocortin MC3 receptor.
The melanocortin MC3 and MC4 receptors are the main melanocortin receptors expressed in brain. Of the endogenous melanocortins, gamma2-melanocortin stimulating hormone (MSH) selectively activates the melanocortin MC3 receptor, whereas alpha- and beta-MSH activate all melanocortin receptors. The aim was to gain an insight into the contribution of amino acids in positions 5 and 10 of melanocortins to the selectivity of [Nle4]Lys-gamma2-MSH for the melanocortin MC3 receptor versus the melanocortin MC4 receptor. Introduction of Asp10 into [Nle4]alpha-MSH as in [Nle4,Gly5,Asp10]alpha-MSH selectively increased the EC50 value for the melanocortin MC4 receptor. Conversely, removal of Asp10, as in [Nle4,Gly10]Lys-gamma2-MSH, selectively decreased the EC50 value for the melanocortin MC4 receptor. Thus, Asp10 in Lys-gamma2-MSH determined selectivity for the melanocortin MC3 receptor versus the melanocortin MC4 receptor.
Oosterom
J
J
Rudolf Magnus Institute for Neurosciences, Medical Faculty, Utrecht University, Netherlands.
Burbach
J P
JP
Gispen
W H
WH
Adan
R A
RA
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001216:Asparagine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018000:Receptors, Peptide / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013329:Structure-Activity Relationship; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D000596:Amino Acids; C104706:MSH, Lys-gamma(2); D010446:Peptide Fragments; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D018000:Receptors, Peptide; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D001216:Asparagine