Secretin at physiological doses inhibits gastric motility via a
vagal afferent pathway.
Lu, Yuanxu, and Chung Owyang.
Gastroenterology Research Unit, Department of Internal Medicine,
The University of Michigan Medical Center, Ann Arbor, MI
APStracts 2:0045G, 1995.
Secretin is an important modulator of gastric motility. In this study
we investigated the site(s) and mechanism(s) of action of secretin to
inhibit gastric motility using an in vivo rat model. Intragastric
pressure response to graded doses of secretin was recorded in
anesthesized rats by a balloon attached to a catheter passed through
an incision in the duodenum into the body of the stomach. The
intragastric pressure was set at 10 cm H2O with balloon distension.
Intravenous infusion of secretin (1.4, 2.8, 5.6, 11.2 and 22.4
pmol/kg/hr) decreased intragastric pressure in a dose-dependent
manner. The threshold dose was 2.8 pmol/kg/hr and the ED50 was 5.6
pmol/kg/hr, which produced physiologic levels of plasma secretin.
Pretreatment with hexamethonium (10 mg/kg) markedly reduced gastric
motor response to secretin (5.6 pmol/kg/hr). Bilateral truncal
vagotomy also significantly diminished gastric motor responses to
secretin. In contrast, secretin (5.6 pmol/kg/hr) had no effect on
gastric contraction evoked by electrical vagal stimulation (1.25-5
Hz) or carbachol (10-6-3x10-5M). These observations indicate that
physiologic concentrations of secretin act via stimulation of
presynaptic cholinergic neurons in a vagally mediated pathway. In
subsequent studies we demonstrated that perivagal treatment 4 days
before with the sensory neurotoxin, capsaicin, abolished gastric
motor response to secretin but did not affect contraction evoked by
electrical vagal stimulation. Similarly, we also showed that
gastroduodenal application of capsaicin for 30 min also markedly
reduced gastric response to secretin. These observations indicate
that physiological doses of secretin act on afferent vagal pathways
originating from the gastroduodenal mucosa to induce gastric
relaxation.
Received 27 May 1994; accepted in final form 6 February 1995.
APS Manuscript Number G203-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.