Serotonin receptor subtypes that depolarize guinea pig inferior mesenteric ganglion neurons

Our previous studies indicated that serotonin (5-HT) depolarized a majority of guinea pig inferior mesenteric ganglion (IMG) neurons and may be another transmitter for the noncholinergic late slow excitatory postsynaptic potential (1s-EPSP) in the IMG. However, the subtypes of 5-HT receptor mediating these responses have not yet been identified. Using intracellular recording, we examined the effect of 5-HT receptor antagonists with specificity to various 5-HT receptor subtypes on the 5-HT-mediated depolarization and 1s-EPSP in IMG neurons in vitro. Cyproheptadine, a 5-HT1/2 receptor antagonist, reversibly inhibited the slow, but not the fast, depolarization and 1s-EPSP in the 5-HT-sensitive neurons. Both mianserin and spiperone, 5-HT2 and 5-HT1A receptor antagonists, did not significantly alter either the fast or slow depolarizing responses or the 1s-EPSP. The 5-HT3 receptor antagonist MDL 72222 (Bemesetron) completely inhibited the fast depolarization with little diminution of the slow depolarization and 1s-EPSP. Superfusion of putative 5-HT1P receptor antagonist, BRL 24924 (Renzapride), reversibly attenuated both the depolarization and 1s-EPSP. However, 5-HT-insensitive neurons with 1s-EPSP were found to be insensitive to both cyproheptadine and BRL 24924. In most 5-HT-sensitive neurons, the 5-HT, receptor agonist, 2-methyl-5-HT, and the selective 5-HT1P agonist, MCPP or 5-OHIP, evoked a fast and a slow depolarization in 55.6 and 71.3% of the neurons, respectively, without a significant effect on the membrane potential in 85.7 and 100% of the 5-HT-insensitive neurons. In 5-HT-sensitive neurons, MDL 72222 reversibly abolished the fast depolarization induced by 2-methyl-5-HT; BRL 24924 significantly inhibited the slow depolarization induced by MCPP or 5-OHIP, but not by SP. Prolonged superfusion of 5-HT-sensitive neurons with MCPP abolished the evoked 1s-EPSP without inhibition of action potential. These results suggest that the fast and slow depolarizations in these neurons are mediated by 5-HT3 and 5-HT1P receptor subtypes, respectively. The latter may also mediate the Is-EPSP in 5-HT-sensitive neurons. (C) 1999 Published by Elsevier Science B.V. All rights reserved.