The gastrokinetic effects of erythromycin: myogenic and neurogenic
mechanisms of action in the rabbit stomach.
Parkman, Henry P., Anthony P. Pagano, Michael A. Vozzelli, James P.
Ryan.
Departments of Medicine and Physiology, Temple University School of
Medicine, Philadelphia, PA
APStracts 2:0076G, 1995.
The aims of these studies were to determine regional differences and
the mechanism of erythromycin's gastric contractile effects. Rabbit
gastric circular muscle strips were studied in vitro. The threshold
dose for erythromycin was significantly less and the maximum
contraction greater in the antrum (1 [mu]M and 0.9+/-0.3 kg/cm2) than
in the fundus (10 [mu]M and 0.3+/-0.1 kg/cm2). Erythromycin-induced
antral contractions were decreased by motilin tachyphylaxis, but
unaffected by tetrodotoxin, atropine, hexamethonium, or ondansetron.
At a subthreshold dose (0.1 [mu]M), erythromycin increased the
frequency, but not amplitude, of bethanechol (10+/-3%) and substance
P (13+/-5%) induced phasic antral contractions. This chronotropic
effect was inhibited with tetrodotoxin, atropine, or motilin
tachyphylaxis. Erythromycin (10 [mu]M) and motilin (1 [mu]M) enhanced
the amplitude of substance P-induced tonic fundic contractions by 38
and 32%, respectively, without effect on bethanechol-induced
contractions. In summary, erythromycin more potently and forcefully
contracts antral than fundic muscle. Erythromycin increases antral
contractility by two mechanisms: an inotropic effect acting on smooth
muscle motilin receptors; and, at lower doses, a cholinergic
chronotropic effect mediated through neuronal motilin receptors.
Received 21 March 1994; accepted in final form 3 April 1995.
APS Manuscript Number G109-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.