Inhibitory effect of theophylline on recombinant GABA(A) receptor.
Convulsions due to systemic toxicity are a major and frequently fatal side effect of theophylline. The cause of theophylline-induced convulsions is not clear, but antagonism of the inhibitory nervous system may be implicated, so we examined the effects of theophylline on GABA-induced currents using recombinant GABA(A) receptor (GABA(A)-R). Theophylline dose-dependently inhibited GABA-induced currents: the IC50 value was 1841+/-63 microM and Hill coefficient 1.09+/-0.03. The inhibitory action of theophylline on GABA-induced currents was competitive and voltage dependent. The inhibition of GABA-induced currents by theophylline may be a primary mechanism underlying theophylline-induced convulsions.
Sugimoto
T
T
Department of Pediatrics, Osaka University Medical School, Suita, Japan.
Sugimoto
M
M
Uchida
I
I
Mashimo
T
T
Okada
S
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000633:toxicity*; D012333:RNA, Messenger / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics; D012640:Seizures / Q000139:chemically induced; D013806:Theophylline / Q000633:toxicity*; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D005680:gamma-Aminobutyric Acid; D013806:Theophylline