Songorine, a diterpenoid alkaloid of the genus Aconitum, is a novel GABA(A) receptor antagonist in rat brain.
Songorine, a diterpenoid alkaloid isolated from the genus Aconitum, was recently found to enhance the excitatory synaptic transmission in rat hippocampus. The mechanism underlying the effects was examined in the present study. The alkaloid at 0.1-300 microM inhibited the specific binding of [(3)H]muscimol to Triton-treated synaptic membranes of rat brain in a concentration-dependent manner (IC(50)=7.06 microM; 95% confidence limits: 3.28-10.84 microM). Scatchard analysis and Lineweaver-Burk double reciprocal plot of [(3)H]muscimol saturation binding data indicate a non-competitive inhibition of the alkaloid on the gamma-aminobutyric acid(A) (GABA(A)) receptor. In acutely dissociated rat hippocampal neurons the alkaloid did not elicit current response, but markedly inhibited the GABA-induced inward current (IC(50)=19.6 microM). The results suggest that songorine is a novel non-competitive antagonist at the GABA(A) receptor in rat brain.
Zhao
Xiao-Yan
XY
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
Wang
Yuan
Y
Li
Yang
Y
Chen
Xue-Qin
XQ
Yang
Hui-Hua
HH
Yue
Jian-Min
JM
Hu
Guo-Yuan
GY
D031841:Aconitum; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D000470:Alkaloids; D004365:Drugs, Chinese Herbal; D018756:GABA Antagonists; D011963:Receptors, GABA-A; C057217:songorine