Increased stress response and beta-phenylethylamine in MAOB-deficient mice.
MAOA and MAOB are key iso-enzymes that degrade biogenic and dietary amines. MAOA preferentially oxidizes serotonin (5-hydroxytryptamine, or 5-HT) and norepinephrine (NE), whereas MAOB preferentially oxidizes beta-phenylethylamine (PEA). Both forms can oxidize dopamine (DA). A mutation in MAOA results in a clinical phenotype characterized by borderline mental retardation and impaired impulse control. X-chromosomal deletions which include MAOB were found in patients suffering from atypical Norrie's disease, which is characterized by blindness and impaired hearing. Reduced MAOB activity has been found in type-II alcoholism and in cigarette smokers. Because most alcoholics smoke, the effects of alcohol on MAOB activity remain to be determined. Here we show that targetted inactivation of MAOB in mice increases levels of PEA but not those of 5-HT, NE and DA, demonstrating a primary role for MAOB in the metabolism of PEA. PEA has been implicated in modulating mood and affect. Indeed, MAOB-deficient mice showed an increased reactivity to stress. In addition, mutant mice were resistant to the neurodegenerative effects of MPTP, a toxin that induces a condition reminiscent of Parkinson's disease.
Grimsby
J
J
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
Toth
M
M
Chen
K
K
Kumazawa
T
T
Klaidman
L
L
Adams
J D
JD
Karoum
F
F
Gal
J
J
Shih
J C
JC
D000818:Animals; D001483:Base Sequence; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000172:deficiency* / Q000235:genetics; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D010084:Oxidation-Reduction; D010627:Phenethylamines / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D013312:Stress, Physiological / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D014960:X Chromosome / Q000235:genetics
D015306:Biogenic Monoamines; D017931:DNA Primers; D010627:Phenethylamines; C029261:phenethylamine; D008995:Monoamine Oxidase