Lutz T A, Rossi R, Althaus J, Del Prete E, Scharrer E
Institute of Veterinary Physiology, University of Zürich, Switzerland.
Peptides. 1998;19(9):1533-40. doi: 10.1016/s0196-9781(98)00114-4.
Amylin and the structurally and functionally related peptide calcitonin gene-related peptide (CGRP) have been shown to reduce food intake in rats. The aim of the present study was to compare the anorectic potency of both peptides over a wide dose range when administered into the lateral brain ventricle (ICV). Furthermore, we also tested the influence of a lesion in the area postrema/nucleus of the solitary tract (AP/NTS) region on the anorectic effects of amylin and CGRP after ICV administration because AP/NTS lesion has been shown to reduce the anorectic effects of both peptides when injected intraperitoneally (IP). Amylin [1-510 pmol/rat (0.004-2 microg/rat) ICV] and CGRP [1-131 pmol/rat (0.004-0.5 microg/rat) ICV] dose-dependently reduced food intake in food-deprived rats. At a dose of 26 pmol/rat (0.1 microg/rat), amylin almost completely suppressed food intake for 1 h after injection. Amylin [EC50 = 2 pmol/rat (0.007 microg/rat)] was markedly more potent than CGRP [57 pmol/rat (0.215 microg/rat)] with regard to its anorectic effect. A lesion in the AP/NTS region did not influence the anorectic effects of amylin and CGRP after administration into the lateral ventricle. It is concluded that amylin is more potent than CGRP in reducing food intake after administration into the lateral brain ventricle. Receptors in the forebrain may mediate the anorectic effects of both peptides when administered via this route.
淀粉样肽以及结构和功能相关的肽降钙素基因相关肽（CGRP）已被证明可减少大鼠的食物摄入量。本研究的目的是比较当将这两种肽注入侧脑室（ICV）时在较宽剂量范围内的厌食效力。此外，我们还测试了孤束核最后区（AP/NTS）区域损伤对ICV注射后淀粉样肽和CGRP厌食作用的影响，因为已表明AP/NTS损伤会降低腹腔注射（IP）时这两种肽的厌食作用。淀粉样肽[1 - 510 pmol/大鼠（0.004 - 2 μg/大鼠）ICV]和CGRP[1 - 131 pmol/大鼠（0.004 - 0.5 μg/大鼠）ICV]剂量依赖性地减少饥饿大鼠的食物摄入量。在剂量为26 pmol/大鼠（0.1 μg/大鼠）时，淀粉样肽在注射后1小时几乎完全抑制食物摄入。就其厌食作用而言，淀粉样肽[EC50 = 2 pmol/大鼠（0.007 μg/大鼠）]比CGRP[57 pmol/大鼠（0.215 μg/大鼠）]明显更有效。AP/NTS区域损伤在注入侧脑室后不影响淀粉样肽和CGRP的厌食作用。得出的结论是，在注入侧脑室后，淀粉样肽在减少食物摄入方面比CGRP更有效。当通过该途径给药时，前脑受体可能介导这两种肽的厌食作用。
