Differential localization of 5-HT1 receptors on myenteric and submucosal neurons

Intracellular recordings were made from guinea pig enteric neurons, and the effects of 5-hydroxytryptamine (5-HT) and the 5-HT1 selective agonists 5-carboxyamidotryptamine (5-CT) and 8-hydroxy-2-(n-dipropylamino)tetralin (DPAT) were studied on membrane potential and synaptic potentials. Most myenteric AH neurons were hyperpolarized when these agonists were applied by superfusion; this hyperpolarization was due to an increase in potassium conductance. Membrane hyperpolarizations to 5-HT, 5-CT, or DPAT were never observed in submucous neurons. Fast nicotinic excitatory postsynaptic potentials (EPSPs) and slow EPSPs recorded from S neurons in the myenteric plexus were suppressed by 5-HT, 5-CT, and DPAT; slow EPSPs in myenteric AH neurons were also inhibited by these agonists. Fast and slow EPSPs recorded from submucous S neurons were not affected by 5-CT or DPAT. However, slow EPSPs recorded from submucous AH neurons were readily blocked by 5-CT and DPAT. The results indicate that 5-HT1 receptors are located on the cell bodies of myenteric but not submucosal neurons. The nerve terminals that release the mediator or mediators of fast and slow synaptic potentials in myenteric neurons also have 5-HT1 receptors and presumably arise from other myenteric neurons; the nerve terminals responsible for the slow EPSP to AH neurons seem to be the only elements of the submucous plexus that express 5-HT1 receptors.