5-Hydroxytryptamine and atropine inhibit nicotinic receptors in submucosal neurons

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 (EC50 = 79 muM) 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 (EC50 = 5 muM) and atropine (EC50 = 1.6 muM), and was unaffected by alpha -bungarotoxin (30 nM). Atropine was less potent in inhibiting the currents induced by 30 muM acetylcholine than those induced by 1 mM acetylcholine. I-ACh was mimicked by the current induced by nicotine (I-Nic;EC50 = 52 muM) I-Nic was also blocked by atropine (EC50 = 1.7 muM) and hexamethonium (EC50 = 3.6 muM). 5-Hydroxytryptamine (5-HT) also inhibited I-ACh in a concentration-dependent manner (EC50 = 180 muM) in the experiments carried out in the presence of a 5-HT3 receptor antagonist. 5-HT had a similar inhibitory effect after the desensitization of 5-HT3 receptors or in neurons with relative small 5-HT3-mediated currents. The inhibitory actions of hexamethonium, atropine, and 5-HT3 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. (C) 2001 Published by Elsevier Science B.V.