Ethanol potentiates ion current mediated by 5-HT3 receptors on neuroblastoma cells and isolated neurons.
Effects of ethanol on receptor/channel complexes appear to play an important role in acute intoxication. One such receptor that has not previously been investigated for ethanol sensitivity is the 5-HT3 receptor for the neurotransmitter serotonin. Ethanol potentiates ion current mediated by 5-HT3 receptors in NCB-20 neuroblastoma cells and isolated Nodose ganglion neurons examined with whole-cell patch-clamp recording. Potentiation increases in a concentration-dependent manner over a range of concentrations (25-100 mM) achieved during acute intoxication. Potentiation appears to be due to a direct effect on the 5-HT3 receptor. Ethanol's effect on 5-HT3 receptor-mediated current decreases with increasing agonist concentration, providing an initial clue as to the mechanism of ethanol's action. These data are discussed in light of recent behavioral data suggesting a role for 5-HT3 receptors in the discriminative stimulus and reinforcing properties of ethanol.
Lovinger
D M
DM
Unit of Synaptic Pharmacology, LPPS, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003472:Curare / Q000633:toxicity; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011985:Receptors, Serotonin; D012701:Serotonin; D000431:Ethanol; D003472:Curare