Erythromycin inhibits rabbit pyloric smooth muscle through neuronal motilin receptors

Back-ground & Aims: Erythromycin's effect in accelerating gastric emptying is attributed primarily to increased antral contractility. The aim of this study was to characterize erythromycin's effect on pyloric muscle. Methods: Rabbit pyloric muscle strips were studied in vitro. Results: Pyloric muscle strips developed spontaneous phasic contractions With a frequency of 1.9 +/- 0.1 contractions per minute. Erythromycin and motilin had dose-dependent inhibitory effects on pyloric muscle, At. the maximal effective dose (50 mu mol/L), erythromycin caused cessation of spontaneous contractions for 1.8 +/- 0.2 minutes, decreasing the initial 2-minute motility index to 35% +/- 9% (P < 0.01) of basal. In the presence of tetrodotoxin, both erythromycin and motilin increased pyloric contractility. Motilin tachyphylaxis both in the presence or absence of tetrodotoxin abolished the effects of erythromycin. The inhibitory effect of erythromycin was decreased by NG-nitro-L-arginine methyl ester and the Vasoactive intestinal peptide antagonist [4-Chloro-D-Phe(6),Leu(17)]vasoactive intestinal peptide, Conclusions: These studies suggest that motilin receptors are present on both pyloric muscle and inhibitory neurons to pyloric muscle, that the primary effect of erythromycin on the pylorus is mediated by activating motilin receptors on inhibitory motor neurons, and that both nitric oxide and vasoactive intestinal peptide may mediate the inhibitory effect of erythromycin.