Direct inhibitory effect of erythromycin on human alimentary tract smooth muscle

Background: Erythromycin was found to stimulate motor activity in the upper gastrointestinal tract. However, in several smooth muscle preparations, it also elicited an inhibitory effect. Our aim was to study the effect of erythromycin in various human alimentary tract smooth muscles. Methods: Using force measurements, we assessed the effect of erythromycin on electrically and chemically evoked contractions of isolated muscle strips of human gallbladder, small intestine, and colon. Results: The muscarinic receptor agonist carbachol evoked contraction in gallbladder, ileum, and colonic smooth muscle that were reduded by erythromycin at 10^-4 M to 72% ± 24%, 77% ± 22%, and 76% ± 22% of control values, respectively. Erythromycin did not affect contractions evoked by noncholinergic agents. Erythromycin's inhibitory effects were not altered by nerve blockade, indicating a direct muscle effect. Eryrthromycin also reduced contractions evoked by electrical stimulation at frequencies of 5, 10, and 20 Hz in the human gallbladder, ileum, and colon preparations. These contractions were reduced by erythromycin in a reversible and dose-dependent manner. Conclusions: Erythromycin antagonized direct cholinergic effects on various smooth muscles from the human alimentary tract in a concentration-dependent manner.