Mountjoy K G, Kong P L, Taylor J A, Willard D H, Wilkison W O
Research Centre for Developmental Medicine and Biology, Department of Paediatrics, School of Biological Sciences, University of Auckland, Auckland 1, New Zealand.
Physiol Genomics. 2001 Feb 7;5(1):11-9. doi: 10.1152/physiolgenomics.2001.5.1.11.
Mouse melanocortin receptors, MC1-R, MC3-R, MC4-R, and MC5-R, when expressed in HEK293 cells and stimulated with either alpha-melanocyte-stimulating hormone (alpha-MSH) or desacetyl-alpha-MSH, mediate increases in intracellular free calcium concentration (Ca(2+)) with EC(50) values between 0.3 and 4.3 nM. The increase in Ca(2+) 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 alpha-MSH (6-fold) and desacetyl-alpha-MSH (8-fold), coupling the mMC1-R to increased Ca(2+). Agouti protein (55 nM) significantly increased the EC(50) for alpha-MSH (3-fold), and 550 nM agouti protein significantly increased the EC(50) for desacetyl-alpha-MSH (4-fold), coupling the mMC4-R to a rise in Ca(2+). 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.
小鼠黑皮质素受体MC1-R、MC3-R、MC4-R和MC5-R，当在HEK293细胞中表达并用α-黑素细胞刺激素（α-MSH）或去乙酰-α-MSH刺激时，介导细胞内游离钙浓度（Ca(2+)）升高，其半数有效浓度（EC(50)）值在0.3至4.3 nM之间。Ca(2+)的升高对霍乱毒素敏感，对百日咳毒素不敏感。其机制涉及从细胞内储存库动员钙，而肌醇三磷酸无短暂升高。小鼠刺鼠蛋白（55 nM）是α-MSH（6倍）和去乙酰-α-MSH（8倍）的竞争性拮抗剂，将mMC1-R与Ca(2+)升高偶联。刺鼠蛋白（55 nM）显著增加α-MSH的EC(50)（3倍），550 nM刺鼠蛋白显著增加去乙酰-α-MSH的EC(50)（4倍），将mMC4-R与Ca(2+)升高偶联。然而，刺鼠蛋白对MC4-R的拮抗作用可能不是竞争性的，因为最大反应也有增加的趋势。刺鼠蛋白（55 nM）对MC3-R和MC5-R无显著拮抗作用。了解黑皮质素肽转导钙信号的生理相关性可能对未来黑皮质素受体治疗靶点的开发很重要。
