Pharmacological analysis of 5-hydroxytryptamine actions on guinea-pig ileal mucosa

The possibility that 5-hydroxytryptamine (5-HT) is involved in the chloride secretory response evoked by electrical stimulation of submucosal neurons was investigated in guinea-pig ileum set up in Ussing flux chambers. When electrical stimulus pulses of 0.5 ms duration, amplitude of 3.2 mA and frequency of 10 Hz were applied repetitively in the plane of the tissue, a biphasic increase in short-circuit current (Isc) occurred. After tachyphylaxis to 5-HT or when the 5-HT antagonist cisapride was present in the bathing solutions, electrical stimulation of enteric nerves still evoked a biphasic change in Isc that was similar in magnitude to the response before either treatment. Cisapride (5 microM) prevented the mucosal response to exogenous 5-HT without altering the functional integrity of the tissues. Addition of 100 microM 5-HT to the submucosal side of the tissue evoked a biphasic increase in Isc that reflected primarily chloride secretion. Tetrodotoxin and atropine significantly reduced but did not abolish the change in Isc and chloride secretion. These results suggest that the mucosal response evoked by electrical field stimulation is not mediated by release of 5-HT at neuro-enterocyte junctions or from endocrine elements. 5-Hydroxytryptamine activated enteric cholinergic neurons within the submucosal plexus to stimulate chloride secretion.