Functional Expression of MT2 (Mel1b) Melatonin Receptors in Human PAZ6 Adipocytes

褪黑素 内科学 内分泌学 褪黑激素受体 受体 脂肪组织 生物 褐色脂肪组织 脂肪细胞 过剩4 松果体 白色脂肪组织 福斯科林 葡萄糖摄取 胰岛素 医学
作者
Lena Brydon,Laurence Petit,Philippe Delagrange,A. Donny Strosberg,Ralf Jockers
出处
期刊:Endocrinology [Oxford University Press]
卷期号:142 (10): 4264-4271 被引量:166
标识
DOI:10.1210/endo.142.10.8423
摘要

Several reports have demonstrated that the pineal hormone, melatonin, plays an important role in body mass regulation in mammals. To date, however, the target tissues and relevant biochemical mechanisms involved remain uncharacterized. As adipose tissue is the principal site of energy storage in the body, we investigated whether melatonin could also act on this tissue. Semiquantitative RT-PCR analysis revealed the expression of MT1 and MT2 melatonin receptor mRNAs in the human brown adipose cell line, PAZ6, as well as in human brown and white adipose tissue. Binding analysis with 2-[125I]iodomelatonin (125I-Mel) revealed the presence of a single, high affinity binding site in PAZ6 adipocytes with a binding capacity of 7.46 ± 1.58 fmol/mg protein and a Kd of 457 ± 5 pm. Both melatonin and the MT2 receptor-selective antagonist, 4-phenyl-2-propionamidotetraline, competed with 2-[125I]iodomelatonin binding, with respective Ki values of 3 × 10−11 and 1.5 × 10−11m. Functional expression of melatonin receptors in PAZ6 adipocytes was indicated by the melatonin-induced, dose-dependent inhibition of forskolin-stimulated cAMP levels and basal cGMP levels with IC50 values of 2 × 10−9 and 3 × 10−10m, respectively. Modulation of the cGMP pathway by melatonin further supports functional expression of MT2 receptors, as this pathway was shown to be specific for that subtype in humans. In addition, long-term melatonin treatment of PAZ6 adipocytes was found to decrease the expression of the glucose transporter Glut4 and glucose uptake, an important parameter of adipocyte metabolism. These results suggest that melatonin may act directly at MT2 receptors on human brown adipocytes to regulate adipocyte physiology.
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