5-HT1A and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic transmission in enteric neurons.
The actions of 5-hydroxtryptamine (5-HT)1A and 5-HT4 receptor agonists on fast excitatory postsynaptic potentials (EPSPs) in myenteric neurons of guinea pig ileum were studied in vitro. Intracellular electrophysiological methods were used to record EPSPs. 5-HT (0.1 microM), 5-carboxamidotryptamine (0.001-0.1 microM), 8-hydroxydipropylaminotetralin (0.003-0.3 microM), and 5-methoxytryptamine (5-MeOT; 0.3 microM) inhibited EPSPs. Agonist inhibition of EPSPs was blocked by the 5-HT1A receptor antagonists, spiperone and NAN-190. In the presence of NAN-190 (0.3 microM), 5-HT (0.001-0.1 microM) increased EPSP amplitude. 5-MeOT (0.001-0.1 microM), renzapride (0.01-0.3 microM), cisapride (0.01-1 microM), and BIMU 8 (0.003-0.1 microM) increased EPSP amplitude but did not change the membrane potential of any neuron. EPSP potentiation induced by each agonist was blocked by the 5-HT3/5-HT4 receptor antagonist, tropisetron (1 microM), but not by the 5-HT3 receptor antagonist, ondansetron (1 microM). Potentiation of fast EPSPs by 5-HT (0.1 microM) desensitized, whereas renzapride (0.1 microM) responses did not. Desensitization induced by BIMU 8 was variable. These data indicate that enteric 5-HT1A and 5-HT4 receptors function to inhibit and facilitate transmitter release, respectively. 5-HT4-mediated facilitation of ganglionic neurotransmission could contribute to the prokinetic effects of cisapride and renzapride.
Pan
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Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Galligan
J J
JJ
D000818:Animals; D004594:Electrophysiology; D006168:Guinea Pigs; D006801:Humans; D007231:Infant, Newborn; D007422:Intestines / Q000294:innervation*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D012701:Serotonin