Raimondi L, Alfarano C, Pacini A, Livi S, Ghelardini C, DeSiena G, Pirisino R
Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.
Br J Pharmacol. 2007 Apr;150(8):1003-10. doi: 10.1038/sj.bjp.0707170. Epub 2007 Mar 5.
Methylamine is an endogenous aliphatic amine exhibiting anorexigenic properties in mice. The aim of this work was to show whether methylamine also modifies feeding behaviour in rats and, if so, to identify the mediator(s) responsible for such effects.
Microdialysis experiments with the probe inserted in the periventricular hypothalamic nucleus were carried out in 12 h starved, freely moving rats. Collected perfusate samples following methylamine injection (i.c.v.) were analysed for nitric oxide by chemiluminescence and for dopamine and 5-hydroxytryptamine content by HPLC. Kv1.6 potassium channel expression was reduced by antisense strategy and this decrease quantified by semi-quantitative RT-PCR analysis.
Methylamine showed biphasic dose-related effects on rat feeding. At doses of 15-30 microg per rat, it was hyperphagic whereas higher doses (60-80 microg) were hypophagic. Methylamine stimulated central nitric oxide (+115% vs. basal) following hyperphagic and dopamine release (60% over basal values) at hypophagic doses, respectively. Treatment with L-N(G)-nitro-L-arginine-methyl ester (i.c.v. 2 microg 10 microl(-1)) or with alpha-methyl-p-tyrosine (i.p. 100 mg kg(-1)) before methylamine injection, reduced nitric oxide output and hyperphagia, or dopamine release and hypophagia respectively. Moreover, hypophagia and hyperphagia, as well as nitric oxide and dopamine release were significantly reduced by down-regulating brain Kv1.6 potassium channel expression.
The effects of methylamine on feeding depend on the hypothalamic release of nitric oxide and dopamine as a result of interaction at the Kv1.6 channels. The study of methylamine levels in the CNS may provide new perspectives on the physiopathology of alimentary behaviour.
甲胺是一种内源性脂肪胺，在小鼠中具有厌食特性。本研究旨在探讨甲胺是否也会改变大鼠的摄食行为，若如此，则确定介导此类作用的介质。
将探针插入室旁下丘脑核进行微透析实验，实验对象为饥饿12小时、自由活动的大鼠。注射甲胺（脑室内注射）后收集的灌流液样本，通过化学发光法分析一氧化氮，通过高效液相色谱法分析多巴胺和5-羟色胺含量。采用反义策略降低Kv1.6钾通道表达，并通过半定量逆转录-聚合酶链反应分析对这种降低进行量化。
甲胺对大鼠摄食呈现双相剂量相关效应。每只大鼠剂量为15 - 30微克时，它会引起摄食亢进，而更高剂量（60 - 80微克）则导致摄食减少。甲胺在摄食亢进时刺激中枢一氧化氮释放（比基础值增加115%），在摄食减少剂量时刺激多巴胺释放（比基础值增加60%）。在注射甲胺前，用L-N(G)-硝基-L-精氨酸甲酯（脑室内注射2微克/10微升）或α-甲基-p-酪氨酸（腹腔注射100毫克/千克）处理，分别降低了一氧化氮释放和摄食亢进，或多巴胺释放和摄食减少。此外，下调脑Kv1.6钾通道表达可显著降低摄食减少和摄食亢进，以及一氧化氮和多巴胺释放。
甲胺对摄食的影响取决于通过与Kv1.6通道相互作用导致的下丘脑一氧化氮和多巴胺释放。对中枢神经系统中甲胺水平的研究可能为饮食行为的生理病理学提供新的视角。
