Inhibitory effects of corymine, an alkaloidal component from the leaves of Hunteria zeylanica, on glycine receptors expressed in Xenopus oocytes.
We previously reported that corymine, an alkaloidal compound extracted from the leaves of Hunteria zeylanica native to Thailand, potentiated convulsions induced by either picrotoxin or strychnine. Therefore, to clarify the mechanism of action of corymine, the effects of corymine on gamma-aminobutyric acid (GABA) and glycine receptors were examined. We used Xenopus oocytes expressing these receptors and the two-electrode voltage-clamp method. The receptors expressed in oocytes injected with rat brain and spinal cord RNA showed the pharmacological properties of GABAA and glycine receptors, respectively. Corymine (1-100 microM) partially (20-30%) reduced the GABA responses in oocytes injected with rat brain RNA, while marked (up to 80%) dose-dependent reductions were observed in the glycine responses in oocytes injected with rat spinal cord RNA. These observations suggest that corymine was more effective against the glycine receptors than the GABA receptors. The ED50 of corymine on the glycine response was 10.8 microM. Corymine, at 30 microM, caused a shift to the right, with a lower maximal response, of the glycine concentration-response curve. This indicated that the action of corymine on glycine receptors is neither competitive nor purely non-competitive. These observations suggest that a binding site other than the glycine recognition site of the glycine receptors is the site of action of corymine.
Leewanich
P
P
Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Japan.
Tohda
M
M
Matsumoto
K
K
Subhadhirasakul
S
S
Takayama
H
H
Aimi
N
N
Watanabe
H
H
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008874:Midazolam / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D018515:Plant Leaves; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D014197:Trees; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000470:Alkaloids; D001640:Bicuculline; D003292:Convulsants; D008874:Midazolam; D010424:Pentobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D005680:gamma-Aminobutyric Acid; C108901:corymine