Block by 5-hydroxytryptamine of neuronal acetylcholine receptor channels expressed in Xenopus oocytes

1. Effects of 5-hydroxytryptamine (5-HT) on neuronal nicotinic acetylcholine (ACh) receptor channels were investigated by expressing cloned channel subunits in Xenopus oocytes. 2. When channels were expressed with a combination of α₃ and β₄ subunits, 5-HT (10 to 300 μM) reversibly inhibited an inward current activated by 100 μM ACh in a concentration-dependent manner. The inhibition was also observed when α₃ subunit was combined with β₂ subunit instead of β₄ subunit, or β₄ subunit was combined with α₂ or α_4-1 subunit instead of α₃ subunit to express channels. 3. Compounds known to antagonize at 5-HT receptors (LY53857, metoclopramide and propranolol) exhibited an agonistic effect: they inhibited the ACh-activated current. 4. The results suggest that 5-HT inhibits recombinant neuronal nicotinic receptor channels through a binding-site distinct from conventional 5-HT receptors. The binding-site may not be attributed to a unique type of channel subunits.