Krasnow Stephanie M, Fraley Gregory S, Schuh Sonya M, Baumgartner James W, Clifton Donald K, Steiner Robert A
Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195-7290, USA.
Endocrinology. 2003 Mar;144(3):813-22. doi: 10.1210/en.2002-220982.
Galanin-like peptide (GALP) shares sequence homology with galanin and binds to galanin receptors in vitro. GALP neurons in the arcuate nucleus coexpress leptin receptors, and GALP mRNA expression is up-regulated by leptin. Based on these observations, we postulated that GALP plays a role in mediating leptin's inhibitory effects on food intake (FI) and body weight (BW), as well as its stimulatory effect on the reproductive axis. To test these hypotheses, we performed several studies in which mice received intracerebroventricular injections of either GALP or vehicle. Acute GALP treatment elicited a dose-dependent suppression of FI and BW. Long-term treatment with GALP caused only transient reductions in FI and BW, demonstrating that the mice became refractory to continued exposure to GALP. GALP inhibited FI as early as 1 h post injection. Central injection of GALP suppressed locomotor activity and elicited the formation of a conditioned taste aversion. In male mice, serum levels of LH and testosterone were increased by GALP administration. Although we cannot rule out possible nonspecific effects of GALP on FI, the present observations are consistent with the argument that GALP is a downstream effector of leptin's actions within the central nervous system.
甘丙肽样肽（GALP）与甘丙肽具有序列同源性，并在体外与甘丙肽受体结合。弓状核中的GALP神经元共表达瘦素受体，且GALP mRNA表达受瘦素上调。基于这些观察结果，我们推测GALP在介导瘦素对食物摄入（FI）和体重（BW）的抑制作用及其对生殖轴的刺激作用中发挥作用。为了验证这些假设，我们进行了多项研究，其中小鼠接受脑室内注射GALP或溶剂。急性GALP处理引起FI和BW的剂量依赖性抑制。长期用GALP处理仅导致FI和BW短暂降低，表明小鼠对持续暴露于GALP产生了耐受性。GALP早在注射后1小时就抑制了FI。中枢注射GALP抑制运动活动并引发条件性味觉厌恶的形成。在雄性小鼠中，给予GALP可提高血清促黄体生成素（LH）和睾酮水平。虽然我们不能排除GALP对FI可能的非特异性作用，但目前的观察结果与GALP是瘦素在中枢神经系统内作用的下游效应器这一观点一致。
