5-Hydroxytryptamine directly inhibits neuronal nicotinic acetylcholine receptors in rat trigeminal ganglion neurons

Abstract: In the present study, whole-cell patch clamp recording technique was used to investigate the action of 5-hydroxytryptamine (5-HT) on the function of native neuronal nicotinic acetylcholine receptors expressed in the rat trigeminal ganglion neurons. Inward currents (I nic) caused by externally-applied nicotine were observed in majority of the examined neurons, which were mediated by α-bungarotoxin-insensitive nicotinic acetylcholine receptors. We found that 5-HT could reversibly inhibit I nic in a concentration-dependent manner, and the inhibition did not involve 5-HT receptors. Other serotonergic agents, such as 2-methyl-5-HT, α-methyl-5-HT, sumatriptan and ICS-205,930, also had similar inhibitory effects on I nic. 5-HT inhibited nicotinic acetylcholine receptors in a non-competitive manner, as 5-HT decreased the maximal current response to nicotine but had no effect on the threshold and EC50. The inhibition of I nic by 5-HT was voltage-dependent and became stronger at hyperpolarized potentials. These results indicated that 5-HT directly inhibited nicotinic acetylcholine receptors in the trigeminal ganglion neurons. As a local modulator of the nicotinic acetylcholine receptor, 5-HT might play a role in the modulation of sensory information. [Copyright &y& Elsevier]