Gehlert D R
Lilly Neuroscience, Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Neuropeptides. 1999 Oct;33(5):329-38. doi: 10.1054/npep.1999.0057.
The 36-amino-acid peptide, neuropeptide Y (NPY), is the most abundant peptide in the rat brain. When administered into the brain, NPY produces a variety of physiological actions including a pronounced stimulation of feeding in satiated rats. Elevations in hypothalamic NPY have been reported after food deprivation and in genetically obese rodents. NPY is believed to produce its actions through a portfolio of G-protein coupled receptors, Y1, Y2, Y4 and Y5. Studies using peptide analogs, receptor knockout animals and specific receptor antagonists suggest the Y1 and Y5 receptors are important in mediating the effects of NPY on food intake in rats. Development of specific receptor antagonists with improved pharmacokinetic properties will be required to determine the importance of NPY in human obesity and appetite disorders.
由36个氨基酸组成的神经肽Y(NPY)是大鼠脑中含量最为丰富的肽。将NPY注入脑内时,它会产生多种生理作用,包括显著刺激饱足大鼠的进食行为。据报道,禁食后以及在遗传性肥胖啮齿动物中,下丘脑的NPY水平会升高。人们认为NPY是通过一组G蛋白偶联受体(Y1、Y2、Y4和Y5)发挥作用的。使用肽类似物、受体敲除动物和特异性受体拮抗剂进行的研究表明,Y1和Y5受体在介导NPY对大鼠食物摄入的影响方面很重要。需要开发具有改善药代动力学特性的特异性受体拮抗剂,以确定NPY在人类肥胖和食欲紊乱中的重要性。