A Direct Inhibitory Effect of Botulinum Toxin Type A on Antral Circular Muscle Contractility of Guinea Pig

Purpose: Recent studies suggest new mechanisms of Botulinum toxin (BoNT) other than inhibiting acetylcholine (ACh) release from nerve terminals. The aim of this study was to determine whether other mechanisms for BoNT exist, so that it directly inhibits smooth muscle contraction. Materials and Methods: Guinea pig antral muscle strips were studied in vitro after 2 hours of exposure to Botulinum toxin type A (BoNT/A). Contractile responses to electric field stimulation (EFS), high K+ (60 mM) and ACh (100 mu M) were evaluated 24 and 48 hours after antral intramuscular injection of BoNT/A or vehicle. Results: BoNT/A inhibited muscular contraction caused by high K+ and ACh. Contractile responses to low (1 & 4 Hz) and high (8 & 20 Hz) frequency EFS of antral muscle strips 24 and 48 hours after antral intramuscular injection of BoNT/A were significantly inhibited. Conclusion: The ability of BoNT/A to directly inhibit antral muscular contractility suggests a new mechanism for the pharmacologic actions of BoNT-direct inhibition of muscular contraction.