5-Hydroxytryptamine and atropine inhibit nicotinic receptors in submucosal neurons

• Published in: European journal of pharmacology 2001-03, Vol.414 (2), p.113-123
• Main Authors: Barajas-López, Carlos, Karanjia, Rustum, Espinosa-Luna, Rosa
• Format: Article
• Language: English
• Subjects: 5-HT (5-hydroxytryptamine, serotonin); 5-HT 3 receptor; Acetylcholine; Acetylcholine - pharmacology; Animals; Atropine; Atropine - pharmacology; Autonomic neuron; Biological and medical sciences; Cholinergic Agents - pharmacology; Electrophysiology; Enteric neuron; Female; Free Radical Scavengers - pharmacology; Fundamental and applied biological sciences. Psychology; Ganglionic Stimulants - pharmacology; Guinea Pigs; Intestine. Mesentery; Ion channel; Ion Channels - drug effects; Ion Channels - physiology; Jejunum - drug effects; Jejunum - physiology; Ligand-gated channel; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Muscarinic Antagonists - pharmacology; Neurons - drug effects; Neurons - physiology; Nicotine - pharmacology; Nicotinic channel; Nicotinic receptor; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - physiology; Serotonin - pharmacology; Submucosal neuron; Submucous Plexus - drug effects; Submucous Plexus - physiology; Vertebrates: digestive system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)00762-2

The whole-cell recording technique was used to investigate the pharmacological properties of acetylcholine-activated ion channels of cultured submucosal neurons from guinea-pig small intestine. Acetylcholine induced whole-cell membrane currents ( I ACh) in a concentration-dependent manner (EC 50=79 μM). I ACh exhibited strong inward rectification, had a reversal potential of +19±2 mV (Na + outside, Cs + inside), was reversibly inhibited in a concentration-dependent manner by hexamethonium (EC 50=5 μM) and atropine (EC 50=1.6 μM), and was unaffected by α-bungarotoxin (30 nM). Atropine was less potent in inhibiting the currents induced by 30 μM acetylcholine than those induced by 1 mM acetylcholine. I ACh was mimicked by the current induced by nicotine ( I Nic; EC 50=52 μM). I Nic was also blocked by atropine (EC 50=1.7 μM) and hexamethonium (EC 50=3.6 μM). 5-Hydroxytryptamine (5-HT) also inhibited I ACh in a concentration-dependent manner (EC 50=180 μM) in the experiments carried out in the presence of a 5-HT 3 receptor antagonist. 5-HT had a similar inhibitory effect after the desensitization of 5-HT 3 receptors or in neurons with relative small 5-HT 3-mediated currents. The inhibitory actions of hexamethonium, atropine, and 5-HT on I ACh were voltage-dependent. Thus, inhibition was significantly smaller for outward currents (recorded at +40 mV) than for inward currents (recorded at −60 mV). Our observations indicate that the I ACh of submucosal neurons are mediated by activation of nicotinic channels, which are blocked by atropine, 5-HT, and hexamethonium. The possibility that one of the 5-HT roles in the gastrointestinal tract might be to directly modulate nicotinic channels is discussed.