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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Raimondi
L
L
Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy.
Alfarano
C
C
Pacini
A
A
Livi
S
S
Ghelardini
C
C
DeSiena
G
G
Pirisino
R
R
D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000378:metabolism*; D001069:Appetite Regulation / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005215:Fasting; D006963:Hyperphagia / Q000378:metabolism / Q000503:physiopathology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D051667:Kv1.6 Potassium Channel / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008297:Male; D008744:Methylamines / Q000008:administration & dosage / Q000378:metabolism*; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D001067:Appetite Depressants; D004791:Enzyme Inhibitors; C064390:Kcna6 protein, rat; D051667:Kv1.6 Potassium Channel; D008744:Methylamines; D016376:Oligonucleotides, Antisense; D009569:Nitric Oxide; D012701:Serotonin; D019805:alpha-Methyltyrosine; C027451:methylamine; D019001:Nitric Oxide Synthase; D014446:Tyrosine 3-Monooxygenase; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine