外因性モノアミンおよび前駆体の脳内取り込みに関する組織化学的研究

HISTOCHEMICAL STUDIES ON THE UPTAKE OF EXOGENOUS MONOAMINES AND THEIR PRECURSORS IN THE RAT BRAIN

I．はじめに

　近年，頭部外筋，脳血管攣縮，脳梗塞，低酸素状態などで，脳内monoamine （MA）が変動することが明らかにされつつあるが，多くの報告では脳内dopamine （DA）が低下すると言われている^14,44）。したがつて，これら病態を有する患者にDAの前駆休のL−3,4—dihydroxy—phenylalanine （L-Dopa）が何らかの治療効果をもたらすことが期待される。著者らも，重症脳損傷後の植物状態患者の意識障害に対してL-Dopa投与を試み，その有効性を示唆する症例のあることを報告した^27,28）。

　しかしながら，外因性のL-Dopaの中枢神経系における作用機序にはまだ不明確な点が多い。またL-Dopaの投与方法に関しても，全身投与されたL-Dopaは多くは末梢で，一部は脳内毛細血管壁でDAに脱炭酸されるため^24,25），L-Dopaの脳内移行は十分とは言えずL-Dopaを直接髄腔内に投与する方法も検討されるべきと思われる。

By means of the histochemical fluorescence method of Falck and Hillarp, the uptake of mono-amines (MA) and their precursors in the brain were studied after their intraperitoneal and intra-ventricular injection into normal, reserpine or reserpine-nialamide pretreated rats. The major findings are as follows.

1) After intraperitoneal injection of L-3, 4- dihydroxyphenyl-alanine (L-Dopa) or L-5-hydroxy-tryptophan (L-5-HTP), a fluorescence was observed in the endothelial cells and pericytes of the capilla-ries, but not after dopamine (DA) or 5-hydroxy-tryptamine (5-HT).

After intraventricular injection of MA or pre-cursors, a diffuse fluorescence was observed close to the ventricles and the ventral part of the sub-arachnoid space, and there were seen fluorescent cells in the capillary walls and atypical small round fluorescent cells which were probably glial cells in these areas.

2) After intraperitoneal injection of L-Dopa, the fluorescence intensity of DA neurons was increased, and after intraventricular injection of L-Dopa, 5-HT cell bodies as well as DA neurons showed an accumulation of green fluorescence.

3) Intraperitoneally or intraventricularly ad-ministered L-5-HTP was taken up by both 5-HT and DA cells.

4) After intraperitoneal injection of DA or 5-HT, uptake was seen in only the areas outside the blood-brain barrier such as the choroid plexus, area postrema and median eminence. However, intra-ventricularly administered 5-HT was accumulated in DA and 5-HT cell bodies, and DA was also observed in DA neurons.

5) No uptake of DA, 5-HT and L-5-HTP was observed in the NA neurons. As an exception, the fluorescence intensity of NA nerve terminals in the nucleus paraventricularis and the ventral part of the nucleus interstitialis striae terminaliswas increased only after intraperitoneal injection of L-Dopa.

6) In addition to the effects on the MA neurons, there was an uptake of intraventricularly injected DA and 5-HT in the cerebellar Purkinje cells, but this was not observed after L-Dopa or L-5-HTP.

The results presented in this study may be important to consider the therapeutic effects, side effects, or both observed in patients receiving high doses of L-Dopa.