Affiliation:
1. Research Centre for Developmental Medicine and Biology, Department of Paediatrics
2. School of Biological Sciences, University of Auckland, Auckland 1, New Zealand
3. Glaxo Wellcome Research Institute, Research Triangle Park, North Carolina 27709
Abstract
Mouse melanocortin receptors, MC1-R, MC3-R, MC4-R, and MC5-R, when expressed in HEK293 cells and stimulated with either α-melanocyte-stimulating hormone (α-MSH) or desacetyl-α-MSH, mediate increases in intracellular free calcium concentration ([Ca2+]i) with EC50 values between 0.3 and 4.3 nM. The increase in [Ca2+]i is cholera toxin sensitive and pertussis toxin insensitive. The mechanism involves calcium mobilization from intracellular stores without a transient rise in inositol trisphosphate. Mouse agouti protein (55 nM) is a competitive antagonist of α-MSH (6-fold) and desacetyl-α-MSH (8-fold), coupling the mMC1-R to increased [Ca2+]i. Agouti protein (55 nM) significantly increased the EC50 for α-MSH (3-fold), and 550 nM agouti protein significantly increased the EC50 for desacetyl-α-MSH (4-fold), coupling the mMC4-R to a rise in [Ca2+]i. However, agouti protein antagonism of the MC4-R may not be competitive since there was a trend for the maximum response to also increase. There was no significant antagonism of the MC3-R and MC5-R by agouti protein (55 nM). Understanding the physiological relevance of the transduction of a calcium signal by melanocortin peptides may be important for future development of therapeutic targeting of the melanocortin receptors.
Publisher
American Physiological Society
Reference38 articles.
1. Receptor-mediated activation of phospholipase A2 and arachidonic acid release in signal transduction
2. Bird GS, Burgess GM, and Putney JWJ. Sulfhydryl reagents and cAMP-dependent kinase increase the sensitivity of the inositol 1,4,5-triphosphate receptor in hepatocytes. J Biol Chem 268: 17917–17923, 1993.
3. High-efficiency transformation of mammalian cells by plasmid DNA.
4. Exocrine Gland Dysfunction in MC5-R-Deficient Mice: Evidence for Coordinated Regulation of Exocrine Gland Function by Melanocortin Peptides
5. Chretien M, Seidah NG, and Dennis M. Processing of precursor polyproteins in rat brain: regional differences in acetylation of POMC peptides. In: Central and Peripheral Endorphins: Basic and Clinical Aspects, edited by Muller EE and Genazzi AR. New York: Raven, 1984, p. 27–58.
Cited by
81 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献