help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mountjoy, K. G.
Right arrow Articles by Wilkison, W. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mountjoy, K. G.
Right arrow Articles by Wilkison, W. O.
Endocrinology Vol. 140, No. 5 2167-2172
Copyright © 1999 by The Endocrine Society

ARTICLES

Agouti Antagonism of Melanocortin-4 Receptor: Greater Effect with Desacetyl-{alpha}-Melanocyte-Stimulating Hormone (MSH) than with {alpha}-MSH

Kathleen G. Mountjoy1, Derril H. Willard and William O. Wilkison2

Research Centre for Developmental Medicine and Biology (K.G.M.), Department of Paediatrics, University of Auckland, Auckland 1, New Zealand; and Glaxo Wellcome Inc. Research Institute (W.O.W., D.H.W.), Research Triangle Park, North Carolina 27709

Address all correspondence and requests for reprints to: Kathleen G. Mountjoy, Research Centre for Developmental Medicine and Biology, Department of Paediatrics, University of Auckland, Auckland 1, New Zealand. E-mail: kmountjoy{at}auckland.ac.nz

Desacetyl-{alpha}-MSH is more abundant than {alpha}-MSH in the brain, the fetus, human blood, and amniotic fluid, but there is little information on its ability to interact with melanocortin receptors. The aim of this study is to compare and contrast the ability of desacetyl-{alpha}-MSH and {alpha}-MSH to couple melanocortin receptors stably expressed in HEK293 cells, to the protein kinase A (PKA) signaling pathway. Desacetyl-{alpha}-MSH activated mouse MC1, MC3, MC4 and MC5 receptors with EC50s = 0.13, 0.96, 0.53, and 0.84 nM, and {alpha}-MSH activated these receptors with EC50s = 0.17, 0.88, 1.05, and 1.34 nM, respectively. Mouse agouti protein competitively antagonized {alpha}-MSH and desacetyl-{alpha}-MSH coupling to the MC1-R similarly. In contrast, mouse agouti protein antagonized desacetyl-{alpha}-MSH much more effectively and potently than {alpha}-MSH coupling the MC4-R to the PKA signaling pathway. Furthermore, mouse agouti protein (10 nM) significantly reduced (1.4-fold) the maximum response of mMC4-R to desacetyl-{alpha}-MSH and 100 nM mouse agouti significantly increased (4.8-fold) the EC50. Minimal antagonism of {alpha}-MSH coupling mMC4-R to the PKA signaling pathway was observed with 10 nM mouse agouti, whereas both 50 and 100 nM mouse agouti appeared to reduce the maximum reponse (1.1- and 1.3-fold, respectively) and increase the EC50 (2.5- and 3.4-fold respectively). Mouse agouti protein did not significantly antagonize either {alpha}-MSH or desacetyl-{alpha}-MSH coupling mouse MC3 and MC5 receptors. Understanding the similarities and differences in activation of melanocortin receptors by desacetyl-{alpha}-MSH and {alpha}-MSH will contribute to delineating the functional roles for these endogenous melanocortin peptides.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. Sanchez, V. C. Rubio, D. Thompson, J. Metz, G. Flik, G. L. Millhauser, and J. M. Cerda-Reverter
Phosphodiesterase inhibitor-dependent inverse agonism of agouti-related protein on melanocortin 4 receptor in sea bass (Dicentrarchus labrax)
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1293 - R1306.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C.-S. J. Wu, D. R. Greenwood, J. M. Cooney, D. J. Jensen, M. A. Tatnell, G. J. S. Cooper, and K. G. Mountjoy
Peripherally administered desacetyl {alpha}-MSH and {alpha}-MSH both influence postnatal rat growth and associated rat hypothalamic protein expression
Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1372 - E1380.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
Y. Zhang, G. E Kilroy, T. M. Henagan, V. Prpic-Uhing, W. G. Richards, A. W. Bannon, R. L. Mynatt, and T. W. Gettys
Targeted deletion of melanocortin receptor subtypes 3 and 4, but not CART, alters nutrient partitioning and compromises behavioral and metabolic responses to leptin
FASEB J, September 1, 2005; 19(11): 1482 - 1491.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. Guo, H. Munzberg, R. C. Stuart, E. A. Nillni, and C. Bjorbaek
N-acetylation of hypothalamic {alpha}-melanocyte-stimulating hormone and regulation by leptin
PNAS, August 10, 2004; 101(32): 11797 - 11802.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. G. Mountjoy, C.-S. Jenny Wu, L. M. Dumont, and J. M. Wild
Melanocortin-4 Receptor Messenger Ribonucleic Acid Expression in Rat Cardiorespiratory, Musculoskeletal, and Integumentary Systems
Endocrinology, December 1, 2003; 144(12): 5488 - 5496.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. J. Clegg, S. C. Benoit, E. L. Air, A. Jackman, P. Tso, D. D'Alessio, S. C. Woods, and R. J. Seeley
Increased Dietary Fat Attenuates the Anorexic Effects of Intracerebroventricular Injections of MTII
Endocrinology, July 1, 2003; 144(7): 2941 - 2946.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
K. G. MOUNTJOY, P. L. KONG, J. A. TAYLOR, D. H. WILLARD, and W. O. WILKISON
Melanocortin receptor-mediated mobilization of intracellular free calcium in HEK293 cells
Physiol Genomics, February 7, 2001; 5(1): 11 - 19.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
D. Chen and A. Garg
Monogenic disorders of obesity and body fat distribution
J. Lipid Res., October 1, 1999; 40(10): 1735 - 1746.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
J. Oosterom, K. M. Garner, W. K. den Dekker, W. A. J. Nijenhuis, W. H. Gispen, J. P. H. Burbach, G. S. Barsh, and R. A. H. Adan
Common Requirements for Melanocortin-4 Receptor Selectivity of Structurally Unrelated Melanocortin Agonist and Endogenous Antagonist, Agouti Protein
J. Biol. Chem., January 5, 2001; 276(2): 931 - 936.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1999 by The Endocrine Society