[Effects of isatin, an endogenous MAO inhibitor, on dopamine (DA) and acetylcholine (ACh) concentrations in rats].
Isatin (indole-2,3-dione), an endogenous inhibitor of monoamine oxidase (MAO), has several physiological properties for stress and anxiety. We previously identified isatin in the brain of stroke-prone spontaneously hypertensive rats (SHRSP) using gas-chromatography mass spectrometry. This study elucidated the effects of isatin on the ACh and DA levels of brain tissues in rats. Furthermore, we evaluated the effect of isatin on DA levels in a rat model of Parkinson's disease induced by Japanese encephalitis virus. Striatal ACh and DA levels significantly increased at 2 hours after isatin (50-200 mg/kg, i.p.) administration. Perfused through a microdialysis probe, isatin (10(-6)-10(-4) M) also produced a significant and concentration-dependent increase in the ACh and DA concentrations in the perfusate from the rat striatum. Furthermore, urinary isatin concentrations in patients with Parkinson's disease tend to increase according to the severity of disease. Isatin (100 mg/kg, i.p.) significantly increased striatal DA levels in a rat model of Parkinson's disease. These results suggest that urinary isatin may become a diagnostic marker for the clinical severity of Parkinson's disease and that endogenous isatin, a new biological modulator, may play a role in the regulation of the brain levels of ACh by increasing the level of DA under stress.
Minami
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
Hamaue
N
N
Endo
T
T
Hirafuji
M
M
Terado
M
M
Ide
H
H
Yamazaki
N
N
Yoshioka
M
M
Ogata
A
A
Tashiro
K
K
D000109:Acetylcholine / Q000032:analysis*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000032:analysis*; D006801:Humans; D007510:Isatin / Q000494:pharmacology* / Q000627:therapeutic use / Q000652:urine; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use / Q000652:urine; D010300:Parkinson Disease / Q000188:drug therapy / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D008996:Monoamine Oxidase Inhibitors; D007510:Isatin; D000109:Acetylcholine; D004298:Dopamine