Azithromycin induced contractile responses of intestinal smooth muscles: A mechanistic approach

Abstract

The current work is documented to investigate the actions of azithromycin on intestinal smooth muscles as there are reports of gastrointestinal upsets with use of azithromycin. Azithromycin was tested on rabbit’s jejunal and rat’s ileal preparations in test concentrations (µM) of 0.01, 0.03, 0.1, 0.3, 1, 3, 5, 10 and 15µM. After mounting the tissues in organ bath containing Tyrode’s solution, spasmogenic activity of azithromycin was observed. To explore its possible mechanisms, response of azithromycin was noted in the presence of 0.3µM atropine, 3µM loratadine, 0.3µM ondansetron, 10µM metoclopramide, 0.3µM verapamil, 1µM propranolol, 3µM amiodarone and combination of 0.3µM each atropine, ondansetron, verapamil and propranolol (AOVP). Mean % Emax for azithromycin was 67.6±1.6 and 54.0±2.1 (% of ACh max) for rabbit’s jejunal and rat’s ileal preparations, respectively. The Mean % Emax for azithromycin in the presence of various antagonists for rabbit’s jejunal and rat’s ileal preparations was as: 2.4±0.1 and 11.4±1.3 with atropine; 67.9±2.0 and 50.7±1.9 with loratadine; 27.5±0.5 and 34.0±2.9 with ondansetron; 88.4±1.2 and 79.1±3.8 with metoclopramide; 13.6±1.2 and 22.3±2.5 with verapamil; 10.2±2.1 and 15.6±1.4 with propranolol; 68.4±1.3 and 58.0±3.4 with amiodarone. Results reveal that the spasmogenic response of azithromycin is mainly mediated through muscarinic receptors. However, we found involvement of mixed pathway including serotonergic receptors, voltage gated calcium channels and voltage gated sodium channels.