AJP - Endocrinology and Metabolism, Vol 271, Issue 4 E669-E677, Copyright © 1996 by American Physiological Society
Gastric antisecretory effect of serotonin: quantitation of release and site of action
K. J. Lepard, J. Chi, J. R. Mohammed, S. Gidener and R. L. Stephens Jr
Department of Physiology, College of Medicine, Ohio State University, Columbus 43210, USA.
Despite many reports that serotonin (5-HT) inhibits gastric acid output,
the role and mechanism of action of endogenous 5-HT to modulate gastric
secretion remain unclear. Vagal stimulation enhanced the basal rate of 5-HT
release into both the gastric lumen (600%) and the portal circulation
(265%) of the rat. The peak rate of 5-HT release into the portal
circulation was 1,000-fold higher that luminal release (12 micrograms/min
and 1.2 ng/min, respectively). To elucidate site(s) of action of 5-HT to
inhibit acid secretion, several approaches were taken. Intraluminal
perfusion of exogenous 5-HT to encompass enhanced levels seen after vagal
stimulation did not reduce gastric acid output. In contrast, administration
of systemic 5-HT, which raised portal venous 5-HT to similar levels as
vagal stimulation, had a marked antisecretory effect. Chemical or surgical
ablation of enteric or sympathetic nerves innervating 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 gastric intra-arterial sodium
nitroprusside, somatostatin monoclonal antibody, or bilateral
adrenalectomy. The results suggest that 5-HT is released from endogenous
stores into the portal circulation in sufficient quantities after vagal
stimulation to alter gastric physiology and that its action is independent
of the autonomic nervous system, gastric mucosal prostaglandins or
somatostatin, mucosal mast cell or adrenal constituents, or changes in
gastric mucosal blood flow.
