Cioni Laura, De Siena Gaetano, Ghelardini Carla, Sernissi Olivia, Alfarano Chiara, Pirisino Renato, Raimondi Laura
Department of Pharmacology, University of Florence, Italy.
Eur J Pharmacol. 2006 Jan 4;529(1-3):179-87. doi: 10.1016/j.ejphar.2005.10.052. Epub 2005 Dec 1.
Previous data indicate that methylamine injection in fasted healthy mice produced a hypophagic effect dependent of neuronal K(v)1.6 channels expression and increased by alpha-aminoguanidine, an inhibitor of semicarbazide-sensitive benzylamine oxidase enzymes mainly involved in amine degradation. In the present work we have investigated: 1) the level of expression and activity of the semicarbazide-sensitive benzylamine oxidase; 2) the effect of methylamine alone and in the presence of alpha-aminoguanidine on food intake of genetic obese and type II diabetes mice (the db/db mice). Db/db mice showed higher levels of semicarbazide-sensitive benzylamine oxidase activities in adipose tissue and in plasma than their lean counterpart (db/db(+) mice). Methylamine (30-75 microg, i.c.v.) showed similar hypophagic effects in obese and lean mice consistently with the levels of neuronal K(v)1.6 found in both animal strains. Alpha-aminoguandine (50 mg/kg, i.p.) increased methylamine (i.c.v.) hypophagia in both obese and lean mice and only in obese mice when methylamine was given i.p. These results suggest a crucial role of semicarbazide-sensitive benzylamine oxidase activity in controlling methylamine hypophagia in hyperphagic diabetic mice.
先前的数据表明,在禁食的健康小鼠中注射甲胺会产生一种依赖于神经元K(v)1.6通道表达的摄食减少效应,并且会被α-氨基胍增强,α-氨基胍是一种主要参与胺降解的氨基脲敏感苄胺氧化酶的抑制剂。在本研究中,我们调查了:1)氨基脲敏感苄胺氧化酶的表达水平和活性;2)单独使用甲胺以及在存在α-氨基胍的情况下对遗传性肥胖和II型糖尿病小鼠(db/db小鼠)食物摄入量的影响。与它们的瘦型对照(db/db(+)小鼠)相比,db/db小鼠在脂肪组织和血浆中的氨基脲敏感苄胺氧化酶活性水平更高。甲胺(30 - 75微克,脑室内注射)在肥胖和瘦型小鼠中均显示出类似的摄食减少效应,这与在两种动物品系中发现的神经元K(v)1.6水平一致。α-氨基胍(50毫克/千克,腹腔注射)在肥胖和瘦型小鼠中均增强了甲胺(脑室内注射)引起的摄食减少,而当甲胺腹腔注射时,仅在肥胖小鼠中增强了这种效应。这些结果表明,氨基脲敏感苄胺氧化酶活性在控制高食欲糖尿病小鼠中甲胺引起的摄食减少方面起着关键作用。