Long-term orexigenic effects of AgRP-(83-132) involve mechanisms other than melanocortin receptor blockade
Long-term orexigenic effects of AgRP-(83-132) involve mechanisms other than melanocortin receptor blockade
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DOI：
10.1152/ajpregu.2000.279.1.r47
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发表时间：
2000-07-01
影响因子：
2.8
通讯作者：
Seeley, RJ
中科院分区：
文献类型：
--
作者：
Hagan, MM;Rushing, PA;Seeley, RJ
内源性黑素皮质素（MC） 3和4受体拮抗剂（MC3/4-R） AgRP过表达可导致肥胖。外源性AgRP（83-132）增加食物摄入，但其持续时间和作用方式尚不清楚。我们在此报告，低至10 pmol的剂量可以在脑室内注射后24小时内对大鼠的食物摄入产生强有力的影响。此外，在大鼠中，单次第三心室剂量低至100 pmol会产生持续一整周的食物摄入量大幅增加。AgRP-(83-132)完全阻断MTII （MC3/4-R激动剂）的厌食作用，同时给予，与竞争性拮抗剂作用一致。然而，当在MTII前24小时给予AgRP-(83-132)时，AgRP-(83-132)对逆转激动剂的厌食作用无效。这些结果支持MC音调在限制食物摄入中的关键作用，并表明AgRP-(83-132)的增氧作用最初是由MC受体的竞争性拮抗介导的，但通过其他机制维持。
Overexpression of agouti-related peptide (AgRP), an endogenous melanocortin (MC) 3 and 4 receptor antagonist (MC3/4-R), causes obesity. Exogenous AgRP(83-132) increases food intake, but its duration and mode of action are unknown. We report herein that doses as low as 10 pmol can have a potent effect on food intake of rats over a 24-h period after intracerebroventricular injection. Additionally, a single third ventricular dose as low as 100 pmol in rats produces a robust increase in food intake that persists for an entire week. AgRP-(83-132) completely blocks the anorectic effect of MTII (MC3/4-R agonist), given simultaneously, consistent with a competitive antagonist action. However, when given 24 h prior to MTII, AgRP-(83-132) is ineffective at reversing the anorectic effects of the agonist. These results support a critical role of MC tone in limiting food intake and indicate that the orexigenic effects of AgRP-(83-132) are initially mediated by competitive antagonism at MC receptors but are sustained by alternate mechanisms.