Effects of antidepressants on serotonin-evoked current in Xenopus oocytes injected with rat brain mRNA.
Serotonin (5-HT, 1 microM) induced an inward current in Xenopus oocytes injected with rat brain mRNA under steady voltage clamp conditions of -60 mV. The 5-HT response was blocked by 0.1 microM mianserin, but neither buspirone, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), trifluoromethylphenyl piperazine (TFMPP), pindolol, propranolol, spiperone, ketanserin nor ICS 205-930 exerted effects, suggesting that the 5-HTIC subtype of 5-HT receptors is involved in the current. The 5-HT-induced current was inhibited by imipramine or desipramine with IC50 values of 60 nM or 20 microM, respectively. The response was also inhibited by setiptilline, maprotiline or amoxapine at a dose of 10 microM. Imipramine at 10 microM had no effect on the acetylcholine (ACh, 1 mM)-induced current response. It has been reported that inositol triphosphate (IP3) formation and intracellular Ca2+ are involved in the 5-HT- as well as ACh-induced current and that intracellular injection of either 50 pmol IP3 or 50 pmol Ca2+ mimics the 5-HT-induced current. The response induced by intracellular injection of either 50 pmol IP3 or 50 pmol Ca2+ was not affected by 10 microM imipramine. It is suggested that imipramine, and perhaps other antidepressant drugs tested, blocks 5-HTIC receptors, subsequently inhibiting the 5-HT-evoked current.
Tohda
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Takasu
T
T
Nomura
Y
Y
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D004594:Electrophysiology; D066298:In Vitro Techniques; D008845:Microinjections; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D011061:Poly A / Q000378:metabolism; D012333:RNA, Messenger / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D014981:Xenopus
D000928:Antidepressive Agents; D012333:RNA, Messenger; D011061:Poly A; D012701:Serotonin; D000109:Acetylcholine