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

• Published in: European journal of pharmacology 2007-11, Vol.574 (2), p.120-126
• Main Authors: Hu, Wang-Ping, Ma, Shi-Yu, Wu, Ji-Liang, Li, Zhi-Wang
• Format: Article
• Language: English
• Subjects: 5-Hydroxytryptamine; Allosteric modulation; Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Female; Medical sciences; Membrane Potentials - drug effects; Neuron; Nicotine - pharmacology; Nicotinic acetylcholine receptor; Nicotinic Antagonists - pharmacology; Pharmacology. Drug treatments; Rat; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - physiology; Receptors, Serotonin - physiology; Serotonin - pharmacology; Trigeminal ganglion; Trigeminal Ganglion - drug effects; Trigeminal Ganglion - physiology; Whole-cell patch clamp technique
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2007.07.037

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 EC 50. 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.