Erythromycin inhibited glycinergic inputs to gastric vagal motoneurons in brainstem slices of newborn rats.
BACKGROUND
Motilin has been known to stimulate the motility of digestive organs peripherally via activation of motilin receptors located at gastrointestinal (GI) cholinergic nerve endings and/or smooth muscle cells. Recent studies have indicated that motilin may also promote GI motility via actions in the central nervous system; however the sites of action and the mechanisms are not clear yet. The present study aimed to test the hypothesis that motilin receptor agonist erythromycin alters the synaptic inputs of preganglionic gastric vagal motoneurons (GVMs) located in the dorsal motor nucleus of the vagus (DMV).


METHODS
Gastric vagal motoneurons were retrogradely labeled by fluorescent tracer from the stomach wall of newborn rats. Fluorescently labeled GVMs in DMV were recorded using whole-cell patch-clamp in brainstem slices and the effects of motilin receptor agonist erythromycin on the synaptic inputs were examined.


RESULTS
Erythromycin (100 nmol L(-1), 1 μmol L(-1), 10 μmol L(-1)) significantly inhibited the frequency of glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) of GVMs and significantly inhibited the amplitude at the concentration of 10 μmol L(-1). These responses were prevented by GM-109, a selective motilin receptor antagonist. In the pre-existence of tetradotoxin (TTX, 1 μmol L(-1)), erythromycin (10 μmol L(-1)) caused significant decreases of the glycinergic miniature inhibitory postsynaptic currents (mIPSCs), in both the frequency and the amplitude. However, erythromycin (10 μmol L(-1)) didn't cause significant changes of the GABAergic sIPSCs.


CONCLUSIONS
Erythromycin selectively inhibits the glycinergic inputs of GVMs.
Liu
H
H
The State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University Shanghai Medical College, Shanghai, China.
Qiu
D
D
Zhou
X
X
Niu
W
W
Qin
X
X
Cai
Y
Y
Wang
J
J
Chen
Y
Y
D000818:Animals; D000831:Animals, Newborn; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena; D004917:Erythromycin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005998:Glycine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009046:Motor Neurons / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects* / Q000294:innervation*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
C093574:GM 109; D006727:Hormone Antagonists; D010456:Peptides, Cyclic; D011500:Protein Synthesis Inhibitors; D005680:gamma-Aminobutyric Acid; D004917:Erythromycin; D005998:Glycine