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Vol. 290, Issue 2, 803-810, August 1999

Synaptic Activation and Properties of 5-Hydroxytryptamine3 Receptors in Myenteric Neurons of Guinea Pig Intestine1

Xiaoping Zhou and James J. Galligan

Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Michigan

The contribution of 5-hydroxytryptamine (serotonin; 5-HT) acting at 5-HT3 receptors to fast excitatory postsynaptic potentials (fEPSPs) and the properties of 5-HT3 receptors in the guinea pig small intestinal myenteric plexus were investigated using electrophysiological methods. In 11% of neurons studied in the acutely isolated myenteric plexus, ondansetron (1 µM) inhibited hexamethonium (100 µM)-resistant fEPSPs. 5-HT elicited an inward current in neurons maintained in primary culture. The peak current reached maximum in <150 ms and desensitized with a double exponential time course (tau 1 = 1.1 ± 0.1 s; tau 2 = 6.9 ± 0.9 s). The whole-cell current/voltage relationship was linear, with a reversal potential of 2.7 ± 1.5 mV. The rapidly activating and desensitizing current was completely blocked by ondansetron (1 µM) and partly inhibited by d-tubocurare (1 µM). The 5-HT3-receptor agonist, 2-methyl-5-HT (100 µM), caused a peak current that was 18% of the peak current caused by 5-HT in the same cells; 2-methyl-5-HT (1 µM) inhibited currents caused by 5-HT. 5-HT-activated single-channel currents in outside-out patches; this response was blocked by ondansetron. The single-channel conductance was 17 ± 1 pS. The single-channel current/voltage relationship was linear between -110 and 70 mV and had a reversal potential near 0 mV. These data indicate that 5-HT contributes to fEPSPs in the myenteric plexus. The 5-HT3 receptor expressed by guinea pig myenteric neurons has pharmacological and electrophysiological properties that distinguish it from 5-HT3 receptors expressed by other autonomic neurons and neurons in the central nervous system.


0022-3565/99/2902-0803$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics



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