Serotonin accumulation in the guinea-pig myenteric plexus: ion dependence, structure-activity relationship and the effect of drugs.

The specific accumulation of serotonin in neurons of the guinea-pig myenteric plexus was examined. Nonadrenergic neurons have been shown to be responsible for this accumulation. Serotonin accumulation, known to be sodium-dependent, was found to be inhibited by elevating the external potassium concentration. Accumulation was inversely related to the concentration of potassium and was also decreased in the presence of 0 mM Ca++ or 12 mM Ca++. The affinity of analogous molecules for the myenteric plexus was greatly reduced in compounds which had no alkyl amino side chain, in which the amino group was methylated or which had no 5-hydroxyl group. Most analogs competitively inhibited serotonin accumulation and 6-hydroxytryptamine was demonstrated by histofluorescence to be taken up into the myenteric plexus after chemical sympathectomy with 6-hydroxydopamine. Serotonin accumulation was also inhibited by tricyclic antidepressants and amphetamines. The inhibition of serotonin accumulation by these compounds differed from their inhibition of accumulation of norepinephrine. As in the central nervous system, chlorimipramine was the most potent tricyclic antidepressant against accumulation of serotonin while desmethylimipramine was the most potent inhibitor of the accumulation of norepinephrine. Amphetamines were more effective inhibitors of serotonin accumulation than were tricyclic antidepressants, but all of these drugs were more effective against the accumulation of norepinephrine than serotonin. This study confirms the existence of a unique population of axons int he mammalian myenteric plexus which are distinguishable by their characteristic accumulation of serotonin and have not been found elsewhere in the peripheral nervous system.