Abstract

The actions of the macrolide antibiotic, erythromycin lactobionate (EM), on nerve-mediated and drug-induced contractions of longitudinal and circular muscle of guinea pig small intestine were studied in vitro. Longitudinal muscle contractions, evoked by single transmural electrical stimuli, were inhibited by EM (10-300 microM) with half-maximal inhibition occurring at 161 microM (EC50). EM-induced inhibition of longitudinal muscle contractions was not affected by the alpha-2 adrenergic antagonist, yohimbine (0.3 microM), by the adrenergic neuronal blocker, guanethidine (10 microM), or the opiate receptor antagonist, naloxone (1.0 microM). Bethanechol-induced longitudinal muscle contractions were also reduced by EM. Noncholinergic longitudinal muscle contractions (1 microM scopolamine present), induced by trains of transmural stimuli, were reduced by EM (EC50, 142 microM); substance P (a mediator of noncholinergic contractions)-induced contractions were also reduced by EM. Circular muscle contractions, evoked by brief trains of transmural stimulation, were inhibited by EM but bethanechol- and substance P-induced contractions of the circular muscle were not altered by EM. Segments (2 cm) of small intestine were used to study reflex circular muscle contractions evoked by distention of the segment aboral to the recording point. Reflex contractions were inhibited by EM (EC50, 84 microM). These data indicate that, in the guinea pig small intestine, EM inhibits nerve-mediated contractions by actions on enteric nerves and on longitudinal but not circular muscle.