Effects of botulinum toxin A on the sphincter of Oddi: an in vivo and in vitro study.
BACKGROUND
Botulinum toxin A is a potent inhibitor of the release of acetylcholine from nerve endings. Local injection of botulinum toxin has recently been suggested to be helpful in sphincter of Oddi dyskinesia by decreasing sphincter of Oddi pressure.


OBJECTIVE
To explore the mechanism of action of botulinum toxin A on sphincter of Oddi (SO) muscle.


METHODS
Four piglets underwent duodenoscopy and SO manometry was performed. After obtaining a baseline pressure, the SO was injected with normal saline and the experiment repeated after one week. The SO was then injected endoscopically with botulinum toxin (40 U) with follow up manometry one week later. The sphincter of Oddi was removed from 10 pigs, cut into three rings, and placed in an organ bath. The force of contraction was measured and registered on a polygraph. Rings were stimulated by 70 V (10 Hz, 0.5 ms) electrical field stimulation for 20 seconds, exogenous acetylcholine (100 microM), and KCl (125 mM). Botulinum toxin (0.1 U/ml) or atropine (1 microM) was added to the incubation medium and the stimulation was repeated.


RESULTS
Mean basal SO pressure in the pigs remained unchanged after saline injection but decreased to about 50% of baseline value following botulinum toxin injection (p = 0.04). The contractions induced by direct stimulation of SO smooth muscle with KCl were not significantly affected by either atropine or botulinum toxin. In all rings exogenous acetylcholine induced contractions, which were totally blocked by atropine, but not by botulinum toxin. Electrical field stimulation induced contractions that were inhibited by both atropine and botulinum toxin.


CONCLUSIONS
Botulinum toxin inhibits pig sphincter of Oddi smooth muscle contractions by a presynaptic cholinergic mechanism, similar to that described in skeletal muscle.
Sand
J
J
Department of Surgery, Tampere University Hospital, Finland.
Nordback
I
I
Arvola
P
P
Pörsti
I
I
Kalloo
A
A
Pasricha
P
P
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D003864:Depression, Chemical; D004558:Electric Stimulation; D008365:Manometry; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009465:Neuromuscular Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D009803:Sphincter of Oddi / Q000187:drug effects*; D013552:Swine
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009465:Neuromuscular Agents; D001285:Atropine; D019274:Botulinum Toxins, Type A; D000109:Acetylcholine