A possible mechanism underlying corymine inhibition of glycine-induced Cl- current in Xenopus oocytes.
We previously reported that corymine, an alkaloid extracted from the leaves of Hunteria zeylanica native to Thailand, inhibited glycine-induced chloride current using a receptor expression model of Xenopus oocytes. In this study, we investigated the mechanism underlying the inhibitory action of this alkaloid on glycine current using the same model. Corymine inhibited glycine current in a noncompetitive fashion. Co-application with strychnine, a competitive glycine receptor antagonist, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a Cl- channel blocker, corymine decreased the ED50 value of strychnine, but did not change that of DIDS. Moreover, the inhibitory effects of corymine and either strychnine or DIDS were additive. The desensitization phase of glycine current showed two exponentials and corymine preferentially inhibited the fast component, whereas strychnine affected both of them to the same extent and DIDS preferentially inhibited the slow component. When these drugs were applied repeatedly, the inhibitory effects of corymine and strychnine were not use-dependent and reversible, while the effect of DIDS was use-dependent and irreversible. The inhibitory effect of corymine on gamma-aminobutyric acid (GABA) current was less potent than the effect on glycine current, while this alkaloid failed to affect acetylcholine and serotonin currents. These results demonstrate that corymine inhibits glycine-gated CI- channels by interacting with the site different from that of DIDS.
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
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002469:Cell Separation; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D002712:Chlorides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018756:GABA Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000378:metabolism; D018684:Glycine Agents / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D013331:Strychnine / Q000494:pharmacology; D014982:Xenopus laevis
D000470:Alkaloids; D018118:Chloride Channels; D002712:Chlorides; D018756:GABA Antagonists; D018684:Glycine Agents; D018009:Receptors, Glycine; C108901:corymine; D013331:Strychnine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D005998:Glycine