Gastric antisecretory effect of serotonin: quantitation of release
and site of action.
Lepard, Kathy J., Jinhan Chi, Jeanette R. Mohammed, Sedef Gidener, and
Robert L. Stephens, Jr.
Department of Physiology, College of Medicine, The Ohio State
University, Columbus, OH 43210
APStracts 3:0124E, 1996.
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 remains 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 1000-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. 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 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.
Received 5 January 1996; accepted in final form 17 June 1996.
APS Manuscript Number E5-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96