Methylamine: a new endogenous modulator of neuron firing?
Increasing evidence suggests that not only ammonia, but also its alkyl-derivatives, including methylamine, may modulate neuron firing. Methylamine occurs endogenously from amine catabolism and its tissue levels increase in some pathological conditions, including diabetes. Interestingly, methylamine and ammonia levels are reciprocally controlled by a semicarbazide-sensitive amine oxidase activity that deaminates methylamine to formaldehyde with the production of ammonia and hydrogen peroxide. As already described for ammonia, methylamine also targets the voltage-operated neuronal potassium channels, probably inducing release of neurotransmitter(s). From this interaction it has been observed that methylamine is 1) hypophagic in mice without producing amphetamine-like effects and 2) a stimulator of nitric oxide release from rat hypothalamus. Methylamine hypophagia is also maintained in genetically obese and diabetic mice and is increased when these animals are pre-treated with -amino guanidine, an inhibitor of methylamine oxidative deamination. The effect of -amino guanidine suggests a potential beneficial effect of this drug, and other such inhibitors, in controlling food intake in animals with disturbed eating behavior. Moreover, the activity of methylamine as an inducer of NO release suggests a role for the amine and for the enzymatic activity that degrades it in neurodegenerative diseases.
Pirisino
Renato
R
Department of Pharmacology, University of Florence, Florence, Italy.
Ghelardini
Carla
C
De Siena
Gaetano
G
Malmberg
Petra
P
Galeotti
Nicoletta
N
Cioni
Laura
L
Banchelli
Grazia
G
Raimondi
Laura
L
D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008744:Methylamines / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism
D008744:Methylamines; D015221:Potassium Channels; D009569:Nitric Oxide; C027451:methylamine