Y. Shiba et al., STIMULATORY MECHANISM OF EM523-INDUCED CONTRACTIONS IN POSTPRANDIAL STOMACH OF CONSCIOUS DOGS, Gastroenterology, 109(5), 1995, pp. 1513-1521
Background & Aims: EM523, a motilin agonist, is intended to be used as
a gastroprokinetic during the postprandial period, but the mechanism(
s) by which EM523 stimulates postprandial contractions in the stomach
has not been studied before. The aim of this study was to examine the
mechanism of contraction-stimulating activity by EM523 in fed dogs. Me
thods: Contractile activity in the gastric antrum of 5 dogs was monito
red using a long-term implanted force transducer and measured by integ
rating the area under the curve. Test materials weve continuously infu
sed or injected intravenously. Results: EM523 (1-30 mu g/kg) induced a
dose-dependent increase in fed-type contractions. EM523-induced contr
actile activity was partially inhibited by atropine, hexamethonium, do
pamine, 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, and substan
ce P antagonist. Atropine-resistant and EM523-induced contractions wer
e further inhibited by 5-HT, receptor antagonist and substance P antag
onist, and the combined use of the two antagonists completely eliminat
ed the atropine-resistant and EM523-induced contractions. Conclusions:
EM523-induced contractions in the fed stomach are quite different fro
m phase III contractions in the fasted state and ave mediated partiall
y through the cholinergic pathway. The noncholinergic pathway involves
5-HT3 and neurokinin 1 receptors.