Methylamine-dependent release of nitric oxide and dopamine in the CNS modulates food intake in fasting rats

Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.
British Journal of Pharmacology (Impact Factor: 4.84). 05/2007; 150(8):1003-10. DOI: 10.1038/sj.bjp.0707170
Source: PubMed


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.

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Available from: Laura Raimondi, Apr 02, 2014
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    • "of the dose as maintenance throughout the second baroreflex curve generation (Abdulla & Johns 2013). This dosage level was comparable to that used previously and reported to non-selectively inhibit brain NOS (Moore et al. 1991, Kadekaro et al. 1998, Dobrucki et al. 2001, Raimondi et al. 2007). "
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    Acta Physiologica 11/2013; DOI:10.1111/apha.12207. · 4.38 Impact Factor
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    • "Studies have shown p-cresol sulfate and indoxyl sulfate to be associated with all-cause mortality, cardiovascular events and endothelial dysfunction in patients with kidney disease [8-12]. Epidemiological studies of MMA and DMA have been fewer, but mouse studies demonstrated that these compounds may be anorectic agents [13-15]. Due to the smaller nature of previous investigations and varying dialysis practices in Europe, we tested the associations between these retained organic solutes and cardiovascular and all-cause mortality in a relatively large, well-characterized cohort of US hemodialysis patients. "
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