Effect of L-arginine on synaptosomal mitochondrial function.
OBJECTIVE
Specific aim of this study is to elucidate the direct effects of L-arginine on the synaptosomal neurotransmission related to the mitochondrial respiratory function.


METHODS
Using isolated endbrains from wild-type mice (ICR), crude synaptosome was analyzed for their concentration of gamma-aminobutyric acid (GABA) and glutamate (Glu) with/without addition of L-arginine. We analyzed the contents of releasing amino acids evoked by high potassium condition and uptake of them in three separated fractions (cytosol, vesicles, and intact mitochondria). The oxygen consumption was also measured by oxygen electrode.


RESULTS
The entire uptakes of GABA and Glu were inhibited by rotenone (about 30 nmol/mg protein) with dose-dependent manner and showed a plateau at about 70% of total uptake. L-arginine inhibited the uptake of Glu logarithmically, however it showed no change in uptake of GABA. The contents of GABA and Glu in synaptosome were decreased in the presence of L-arginine. L-arginine enhanced the respiration of state II by succinate on synaptosomal respiration, although the respiration of synaptosomal mitochondrial fraction and the respiratory chains enzyme activities were almost unaffected by L-arginine. In the presence of rotenone, L-arginine decreased the uptake of Glu without changing the uptake of GABA, increased the releasing of GABA, and may modulate the excitability of neuronal state on the cytosol, cytomembrane, and/or organelles except for mitochondria.


CONCLUSIONS
L-arginine may modulate excitation by neurotransmitters at nerve endings, in relation to potentiated respiratory metabolism of succinate in synaptosomes. Such effects might contribute to alleviation of stroke-like symptoms in MELAS.
Hirata
Koji
K
Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan.
Akita
Yukihiro
Y
Povalko
Nataliya
N
Nishioka
Junko
J
Yatsuga
Shuichi
S
Matsuishi
Toyojiro
T
Koga
Yasutoshi
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D017241:MELAS Syndrome / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D019802:Succinic Acid / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000493:pharmacokinetics
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001120:Arginine; D019802:Succinic Acid; D011188:Potassium