On the mechanism of pyridoxal phosphate-related convulsions as implicated in enhanced transport of GABA

Abstract

The intracisternal injection of pyridoxine or pyridoxal phosphate has been shown to result in status epilepticus, which is preventable or reversible by GABA. Since pyridoxal phosphate and pyridoxamine phosphate serve as coenzymes for glutamic acid decarboxylase and γ-aminobutyric acid α-ketoglutarate transaminase respectively, and since alteration in GABA level produces convulsions, the effect of Vitamin B 6 on the uptake of GABA in synaptosomes was investigated. It was found that the B 6 vitamers, pyridoxal, pyridoxamine, pyridoxal phosphate or pyridoxamine phosphate; the vitamin B 6 antimetabolite such as deoxypyridoxine; and the vitamin B 6 depletors namely, cycloserine or isoniazid failed to alter the uptake of GABA into synaptosomes isolated from either the cerebral cortex or the hippocampus. On the other hand, pyridoxal or pyridoxal phosphate in a concentration of 1 mM enhanced GABA uptake in nuclear free crude homogenates of the cerebral cortex. These results do not support the direct involvement of B 6 derivatives in the transport of GABA. The effect of pyridoxal phosphate on the specific binding of GABA may clarify further the mechanism of pyridoxal phosphate-related convulsions