Harrold J A, Williams G, Widdowson P S
Department of Medicine, University of Liverpool, Liverpool, United Kingdom.
Biochem Biophys Res Commun. 1999 May 19;258(3):574-7. doi: 10.1006/bbrc.1999.0675.
Melanocortin-4 receptor (MC4-R) density is thought to be regulated by synaptic availability of endogenous agonist, alpha-melanocyte-stimulating hormone (alpha-MSH), and also by agouti-related protein (AGRP), which acts as a competitive antagonist. As hypothalamic MC4-R have been implicated in the regulation of energy balance, we examined concentrations of alpha-MSH and AGRP in hypothalami of dietary-obese and food-restricted rats. In dietary-obese rats, AGRP concentrations were significantly increased by 43% (p < 0.01) above lean controls, whereas a 91% (p < 0.01) reduction was observed in food-restricted rats. Surprisingly, hypothalamic concentrations of alpha-MSH and its precursor peptide, pro-opiomelanocortin (POMC), did not differ significantly from controls in either model. In conclusion, we suggest that MC4-R activity may not be regulated by changes in agonist (alpha-MSH) but by changes in the antagonist (AGRP) availability, which may modulate background activation of the receptor by tonic alpha-MSH release. AGRP may be an important modulator of feeding behaviour.
黑皮质素-4受体（MC4-R）的密度被认为受内源性激动剂α-黑素细胞刺激素（α-MSH）的突触可用性调节，同时也受作为竞争性拮抗剂的刺鼠相关蛋白（AGRP）调节。由于下丘脑MC4-R与能量平衡的调节有关，我们检测了饮食诱导肥胖和食物限制大鼠下丘脑内α-MSH和AGRP的浓度。在饮食诱导肥胖的大鼠中，AGRP浓度比瘦素对照组显著增加了43%（p < 0.01），而在食物限制的大鼠中观察到AGRP浓度降低了91%（p < 0.01）。令人惊讶的是，在这两种模型中，下丘脑内α-MSH及其前体肽阿黑皮素原（POMC）的浓度与对照组相比均无显著差异。总之，我们认为MC4-R的活性可能不受激动剂（α-MSH）变化的调节，而是受拮抗剂（AGRP）可用性变化的调节，这可能通过持续性α-MSH释放来调节受体的背景激活。AGRP可能是进食行为的重要调节因子。
