GASTRIC ANTISECRETORY EFFECT OF SEROTONIN - QUANTITATION OF RELEASE AND SITE OF ACTION

Despite many reports that serotonin (5-HT) inhibits gastric acid outpu t, the role and mechanism of action of endogenous 5-HT to modulate gas tric secretion remain unclear. Vagal stimulation enhanced the basal ra te of 5-HT release into both the gastric lumen (600%) and the portal c irculation (265%) of the rat. The peak rate of 5-HT release into the p ortal circulation was 1,000-fold higher that luminal release (12 mu g/ min and 1.2 ng/min, respectively). To elucidate site(s) of action of 5 -HT to inhibit acid secretion, several approaches were taken. Intralum inal perfusion of exogenous 5-HT to encompass enhanced levels seen aft er vagal stimulation did not reduce gastric acid output. In contrast, administration of systemic 5-HT, which raised portal venous 5-HT to si milar levels as vagal stimulation, had a marked antisecretory effect. Chemical or surgical ablation of enteric or sympathetic nerves innerva ting the stomach did not attenuate the inhibitory effect of exogenous 5-HT on gastric acid output. The antisecretory effect of systemic 5-HT was insensitive to pretreatment with piroxicam, doxantrazole, close g astric intra-arterial sodium nitroprusside, somatostatin monoclonal an tibody, or bilateral adrenalectomy. The results suggest that 5-HT is r eleased from endogenous stores into the portal circulation in sufficie nt quantities after vagal stimulation to alter gastric physiology and that its action is independent of the autonomic nervous system, gastri c mucosal prostaglandins or somatostatin, mucosal mast cell or adrenal constituents, or changes in gastric mucosal blood flow.