Effect of 5-hydroxyindole on ethanol potentiation of 5-hydroxytryptamine (5-HT)3 receptor-activated ion current in NCB-20 neuroblastoma cells.
We examined the effect of 5-hydroxyindole (5-HI) on the potentiation of 5-hydroytryptamine (5-HT)(3) receptor function by ethanol (EtOH) so as to study whether EtOH potentiates channel function through increasing activation or blocking desensitization. We measured 5-HT(3) receptor current using a whole-cell voltage clamp technique with a method of rapid drug application in NCB-20 neuroblastoma cells. The 5-HI, an agent that block receptor desensitization, increased the decay time constant (tau), not the peak of 5-HT(3) receptor-mediated currents induced by 10 microM 5-HT. EtOH did not change the peak amplitude and tau of the current induced by 10 microM 5-HT. Coapplication of EtOH and 5-HI with 5-HT caused no increase in the peak currents, but tau was further increased. Therefore, a further block in desensitization could be induced by 5-HI, despite the presence of EtOH. These results indicate that EtOH potentiates 5-HT(3) receptor function, with these effects due at least in part by increasing channel activation rather than by blocking desensitization.
Yang
Han Soo
HS
Department of Pharmacology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, South Korea.
Kim
Seong Yun
SY
Choi
Se Joon
SJ
Kim
Ki-Jung
KJ
Kim
Ok Nyu
ON
Lee
Sang Bok
SB
Sung
Ki-Wug
KW
D000818:Animals; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007473:Ion Channels / Q000502:physiology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007211:Indoles; D007473:Ion Channels; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; C026785:5-hydroxyindole; D012701:Serotonin; D000431:Ethanol