Effects of serotonin on acid secretion in isolated rat stomach: The role of 5-HT ₃ receptors

Serotonin (5-hydroxytryptamin; 5-HT) content has been measured using high-performance liquid chromatography with electrochemical detection (HPLC-ECD). The distributions of 5-HT-containing cells and 5-HT₃ receptors have been determined with specific antibodies against 5-HT and 5-HT₃ receptors, respectively. The effect of serotonin on acid secretion has been studied using an isolated rat stomach model. It has been shown that 5-HT concentrations in the fundus, mucosal layers of the corpus, remaining layer of the corpus and antrum are approximately 152, 498, 1494 and 972 nmol/mg protein, respectively. The distribution of 5-HT-containing cells is concentrated in the enteric plexus and enterochromaffin (EC) cells in the deep mucosal layer. Immunoreactivity to 5-HT₃ receptors is localized in numerous neurons of the myenteric and submucosal plexus and concentrated in the neuronal plasma membrane, submucosa, endocrine cells and lamina propria. In the present study, the effect of 5-HT on gastric acid secretion was investigated on an everted preparation of isolated rat stomach. 5-HT at 1-100 μM reduced acid secretion stimulated by oxotremorine while 10 μM 5-HT did not modify the basal secretion of gastric acid. We further showed that 10 μM 5-HT reduced acid secretion and pepsin output stimulated by oxotremorine, histamine and pentagastrin; among the 5-HT receptors agonists tested, 2-methyl-5-HT (1-10 μM), a 5-HT₃ receptor agonist, inhibited oxotremorine-, histamine- and pentagastrin-stimulated acid secretions, and this inhibitory effect was blocked by 1 μM MDL 72222, a specific 5-HT₃ receptor antagonist. These results suggest that 5-HT is released from serotoninergic neurons, their processes and EC cells. The effect of 5-HT mediated by 5-HT₃ receptors involves distinct neuronal and non-neuronal pathways which modulate gastric acid secretion.