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Am J Physiol Gastrointest Liver Physiol 285: G291-G297, 2003. First published March 26, 2003; doi:10.1152/ajpgi.00296.2002
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NEUROREGULATION AND MOTILITY

Inhibitory effects of botulinum toxin on pyloric and antral smooth muscle

Arlene N. James, James P. Ryan, and Henry P. Parkman

Departments of Medicine and Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

Submitted 22 June 2002 ; accepted in final form 18 March 2003

Botulinum toxin injection into the pylorus is reported to improve gastric emptying in gastroparesis. Classically, botulinum toxin inhibits ACh release from cholinergic nerves in skeletal muscle. The aim of this study was to determine the effects of botulinum toxin on pyloric smooth muscle. Guinea pig pyloric muscle strips were studied in vitro. Botulinum toxin type A was added; electric field stimulation (EFS) was performed every 30 min for 6 h. ACh (100 µM)-induced contractile responses were determined before and after 6 h. Botulinum toxin caused a concentration-dependent decrease of pyloric contractions to EFS. At a low concentration (2 U/ml), botulinum toxin decreased pyloric contractions to EFS by 43 ± 9% without affecting ACh-induced contractions. At higher concentrations (10 U/ml), botulinum toxin decreased pyloric contraction to EFS by 75 ± 7% and decreased ACh-induced contraction by 79 ± 9%. In conclusion, botulinum toxin inhibits pyloric smooth muscle contractility. At a low concentration, botulinum toxin decreases EFS-induced contractile responses without affecting ACh-induced contractions suggesting inhibition of ACh release from cholinergic nerves. At higher concentrations, botulinum toxin directly inhibits smooth muscle contractility as evidenced by the decreased contractile response to ACh.

gastroparesis; gastrointestinal smooth muscle


Address for reprint requests and other correspondence: H. P. Parkman, Gastroenterology Section, Dept. of Internal Medicine, Temple University School of Medicine, Parkinson Pavilion, 8th floor, 3401 N. Broad St., Philadelphia, PA 19140 (E-mail: henry.parkman{at}temple.edu).






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