Electrophysiological characterization of a motilin agonist gm 611
on duodenal smooth muscle from the rabbit.
Yamada, Kazunori, Shan Chen, Nor A. Abdullah, Masao Tanaka, Yushi Ito,
and Ryuji Inoue.
Department of Pharmacology and the first Department of Surgery,
Faculty of Medicine, Kyushu University, Fukuoka 812-82, JAPAN
APStracts 3:0142G, 1996.
Effects of motilin and a newly synthesized erythromycin derivative,
GM611, on the membrane potential and currents of rabbit duodenal
smooth muscle have been investigated by intracellular potential
recording and whole-cell patch clamp technique, and compared with
results from contractile experiments. Motilin and GM611 (0.01-100nM)
produced slowly sustained depolarizations dose-dependently (ED50s =
0.15 and 3.9nM for motilin and GM611, respectively), but exhibited
biphasic effects on the spike activities superimposed on slow waves.
With small depolarizations, the number of spike discharges increased,
whereas larger depolarizations markedly reduced the spike amplitude.
The motilin (or GM611)-induced depolarization appeared to be
associated with the activation of monovalent cation-selective
channels, and the reduction in the spike amplitude mainly with
inhibition of voltage-dependent Ca channels. Furthermore, data from
patch clamp experiments suggested that Ca release occurred from
heparin-sensitive internal stores upon stimulation of motilin
receptors by these agonists. Possible implications of these
electrophysiological effects in motilin- or GM611-induced tonic and
phasic contractions has been discussed.
Received 4 March 1996; accepted in final form 25 June 1996.
APS Manuscript Number G84-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996