血清素
受体
胆固醇
内分泌学
内科学
HMG-CoA还原酶
低密度脂蛋白受体
化学
他汀类
光漂白后的荧光恢复
药理学
5-羟色胺受体
生物化学
生物
还原酶
医学
酶
脂蛋白
膜
作者
SK Shrivastava,Thomas J. Pucadyil,Yamuna Devi Paila,Sourav Ganguly,Amitabha Chattopadhyay
出处
期刊:Biochemistry
[American Chemical Society]
日期:2010-06-03
卷期号:49 (26): 5426-5435
被引量:136
摘要
Statins are potent inhibitors of HMG-CoA reductase, the key rate-limiting enzyme in cholesterol biosynthesis, and are some of the best selling drugs globally. We have explored the effect of chronic cholesterol depletion induced by mevastatin on the function of human serotonin1A receptors expressed in CHO cells. An advantage with statins is that cholesterol depletion is chronic which mimics physiological conditions. Our results show a significant reduction in the level of specific ligand binding and G-protein coupling to serotonin1A receptors upon chronic cholesterol depletion, although the membrane receptor level is not reduced at all. Interestingly, replenishment of mevastatin-treated cells with cholesterol resulted in the recovery of specific ligand binding and G-protein coupling. Treatment of cells expressing serotonin1A receptors with mevastatin led to a decrease in the diffusion coefficient and an increase in the mobile fraction of the receptor, as determined by fluorescence recovery after photobleaching measurements. To the best of our knowledge, these results constitute the first report describing the effect of chronic cholesterol depletion on the organization and function of a G-protein-coupled neuronal receptor. Our results assume significance in view of recent reports highlighting the symptoms of anxiety and depression in humans upon statin administration, and the role of serotonin1A receptors in anxiety and depression.
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