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 μM) 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 and 4 Hz) and high (8 and 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.