Effect of Guanidino Compounds on GABA-Stimulated Chloride Influx into Membrane Vesicles from Rat Cerebral Cortex

Abstract

More than one hundred guanidino compounds are known to occur naturally, and the physiological role of some these compounds has been elucidated1. Since some of the guanidino compounds have the ability to induce seizures or convulsions in animals, it has been suggested that guanidino compounds may play a role in neurological disorders such as epilepsy and tetanus. Recently, electrophysiological studies indicated that guanidino compounds such as γ- guanidinobutyric acid, guanidinoethanesulfonic acid and δ-guanidinovaleric acid induced spike discharges on the electroencephalogram2–5. Furthermore, spike discharges induced by δ-guanidinovaleric acid were antagonized by γ- aminobutyric acid (GABA) and muscimol, suggesting that δ-guanidinovaleric acid may be an endogeneous GABA receptor antagonist5. GABA is known to be an inhibitory neurotransmitter in the mammalian central nervous system and to exert its effect by increasing chloride conductance in neuronal membranes. In spite of cumulative evidence that convulsants such as bicuculline, piero- toxin, t-butylbicyclophosphorothionate and neuroinsecticides inhibit the GABA-gated chloride channel6–7, it is unknown whether guanidino compounds have influence on the GABA-gated chloride channel. Thus, to elucidate the mechanism of action of the guanidino compounds, by the use of a newly developed method6, we examined the effect of ten guanidino compounds possessing convulsant activity on GABA-stimulated 36C1- uptake by membrane vesicles from rat cerebral cortex.