Vigabatrin inhibits pyridoxine-5'-phosphate oxidase, not pyridoxal kinase in the hippocampus of seizure prone gerbils.
To identify the effects of vigabatrin (VGB) on the metabolism of pyridoxal 5'-phosphate (PLP) in the seizure prone gerbil hippocampus, we conducted a chronological and comparative analysis of pyridoxal kinase (PLK) and pyridoxine-5'-phosphate oxidase (PNP oxidase) expression. In the VGB treated animals, PNP oxidase immunoreactivity was reduced, although the distribution and immunodensity of PLK were unaltered, as compared with control animals. In a Western blot study, the densities of PNP oxidase immunoreactivities in VGB treated animals were found to have decreased significantly. However, no differences in PLK immunoreactive bands were observed in controls or in VGB treated animals. By enzyme activity assay, and in contrast to PLK, the specific activity of PNP oxidase in the VGB treated gerbils was significantly reduced. In conclusion, the present data presents a piece of in vivo evidence that supports the anti-epileptic effects mediated by pyridoxamine-5'-phosphate (PMP) metabolism, and which may be helpful in the development of an anti-epileptic drug.
An
Sung-Jin
SJ
Department of Anatomy, College of Medicine, Hallym University, Kangwon-Do 200-702, Chunchon, South Korea.
Park
Seung-Kook
SK
Hwang
In Koo
IK
Choi
Soo-Young
SY
Kwon
Oh-Shin
OS
Won
Moo Ho
MH
Kang
Tae-Cheon
TC
D000818:Animals; D015153:Blotting, Western; D003720:Densitometry; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007150:Immunohistochemistry; D011731:Pyridoxal Kinase / Q000378:metabolism*; D011734:Pyridoxaminephosphate Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012640:Seizures / Q000201:enzymology* / Q000235:genetics; D020888:Vigabatrin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011734:Pyridoxaminephosphate Oxidase; D011731:Pyridoxal Kinase; D020888:Vigabatrin