Orthosteric and Allosteric Activation of Human 5-HTA Receptors.

The serotonin type 3 receptor (5-HT) is a ligand-gated ion channel that converts the binding of the neurotransmitter serotonin (5-HT) into a transient cation current that mediates fast excitatory responses in peripheral and central nervous systems. Information regarding the activation and modulation of the human 5-HT type A receptor has been based only on macroscopic current measurements because of its low ion conductance. By constructing a high-conductance human 5-HTA receptor, we here revealed mechanistic information regarding the orthosteric activation by 5-HT and by the partial agonist tryptamine, and the allosteric activation by the terpenoids, carvacrol, and thymol.