Inhibitory effects of botulinum toxin on 5-HT1C receptor-induced Cl- current in Xenopus oocytes.
Several low molecular weight G proteins have been identified, but their functional roles remain unclear. To clarify the involvement of low molecular weight G protein in receptor-stimulated turnover of polyphosphoinositide (PI) turnover, influences of botulinum toxins on serotonin (5-HT)-stimulated Cl- current mediated by PI turnover were investigated using Xenopus oocytes injected with rat brain mRNA. Treatment with botulinum toxin C, D or purified ADP-ribosyltransferase of botulinum toxin (botulinum toxin C3 enzyme) inhibited the 5-HT-induced Cl- current in oocytes, and ADP-ribosylated 23 kDa proteins. Both botulinum toxin C3 enzyme-induced inhibition of the current and ADP-ribosylation were suppressed by pretreatment with antibotulinum toxin C3 enzyme antibody. Botulinum toxin D treatment of oocytes was ineffective in the response of Cl- current induced by injection of 50 pmol inositol 1,4,5-trisphosphate and 50 pmol Ca2+. It is suggested that low molecular weight G proteins ADP-ribosylated by botulinum toxin C3 enzyme are involved in phospholipase C activation in Xenopus oocytes.
Tohda
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Takasu
T
T
Nakamura
J
J
Morii
N
N
Narumiya
S
S
Nomura
Y
Y
D036002:ADP Ribose Transferases / Q000494:pharmacology*; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008297:Male; D009865:Oocytes / Q000187:drug effects; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D014982:Xenopus laevis
D002712:Chlorides; D018129:Phosphatidylinositol Phosphates; D011985:Receptors, Serotonin; D012701:Serotonin; D015544:Inositol 1,4,5-Trisphosphate; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D011065:Poly(ADP-ribose) Polymerases; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D002118:Calcium