Electrophysiological characterization of a motilin agonist, GM611, on rabbit duodenal smooth muscle.
Effects of motilin and a newly synthesized erythromycin derivative, GM611, on 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 (0.01-100 nM) dose dependently produced slowly sustained depolarizations (half-maximal effective dose = 0.15 and 3.9 nM for motilin and GM611, respectively) but exhibited biphasic effects on spike activities superimposed on slow waves. With small depolarizations, the number of spike discharges increased, whereas larger depolarizations markedly reduced spike amplitude. Motilin-induced (or GM611-induced) depolarization appeared to be associated with the activation of monovalent cation-selective channels, and the reduction in the spike amplitude appeared mainly to be associated with inhibition of voltage-dependent Ca2+ channels. Furthermore, data from patch-clamp experiments suggested that Ca2+ 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 have been discussed.
Yamada
K
K
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Chen
S
S
Abdullah
N A
NA
Tanaka
M
M
Ito
Y
Y
Inoue
R
R
D000818:Animals; D004386:Duodenum / Q000502:physiology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D008297:Male; D009037:Motilin / Q000819:agonists*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011817:Rabbits
D005765:Gastrointestinal Agents; D009037:Motilin; D004917:Erythromycin; C103741:mitemcinal