Effect of penicillin on GABA-gated chloride ion influx.
To investigate the mechanism of penicillin-induced convulsions, we have studied the effects of penicillin G (PC-G) on GABA-gated chloride ion influx in brain 'microsac' preparations of mice. In the presence of 10(-4) M GABA, PC-G inhibited GABA-gated chloride ion influx in a dose-dependent manner. The dose-response curve for GABA in the presence of 10(-3) M PC-G was shifted rightward and there was a decrease in maximum response. The inhibitory effects of PC-G were not reversed by RO 15-1788, an antagonist of benzodiazepine (BZ) receptors, but were reversed by washing the 'microsac' membranes. Therefore, PC-G probably exerts its proconvulsant effect by inhibiting GABA-gated chloride ion influx. However, it appears not to act through the BZ receptor of the GABA/BZ receptor complex.
Tsuda
A
A
Department of Pediatrics, Shimane Medical University, Izumo, Japan.
Ito
M
M
Kishi
K
K
Shiraishi
H
H
Tsuda
H
H
Mori
C
C
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D010400:Penicillin G / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018118:Chloride Channels; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D010400:Penicillin G