Serotonin receptors on submucous neurons in guinea pig colon

Intracellular microelectrodes were used to investigate the neuropharmacology of 5-hydroxytryptamine (5-HT) in the submucous plexus of the distal colon of the guinea pig. Three effects resulted from application of 5-HT to submucous neurons. Two of the effects were components of a biphasic depolarization mediated by receptors on the neuronal cell body. The third was suppression of acetylcholine release at nicotinic synapses on the cell bodies and was mediated by presynaptic 5-HT receptors. The initial component of the biphasic depolarization was a rapidly activating response characterized by increased ionic conductance and a tendency for rapid desensitization. Pharmacological analysis with selective agonists and antagonists suggested mediation of this response by the 5-HT₃ receptor subtype. The second component of the depolarizing response was a slowly activating and long-lasting depolarization associated with decreased ionic conductance. Analysis of this response suggested it was mediated by the 5-HT(1P) receptor subtype. Identification of the presynaptic receptors for 5-HT was equivocal. These receptors did not behave like 5-HT₃ or 5-HT(1P) receptor subtypes. The putative 5-HT₄ agonist 5-methoxytryptamine was equipotent with 5-HT in producing presynaptic inhibition at the fast nicotinic synapses.