Antispasmodic effect of amiodarone on gastrointestinal smooth muscle: possible involvement of calcium.
The influence of amiodarone on contractions induced by acetylcholine (ACh) was studied in isolated preparations of guinea-pig ileum, duodenum and stomach fundus as well as in rat stomach fundus. In the guinea-pig ileum a concentration-dependent antispasmodic effect of amiodarone (20-70 microM) was observed after 30 min exposure to the drug, but not after 15 min. The inhibition of ACh-induced contraction further increased with time after removal of amiodarone from the bathing fluid. Similar results were obtained in ileum preparations maintained in a low Ca2+ medium (0.35 mM CaCl2) and under these conditions the response to ACh was restored by washing the tissue with a normal Ca2+ medium (1.4 mM CaCl2). Both low Ca2+ and amiodarone depressed the tonic component of ACh-induced contraction more than the phasic one. Guinea-pig duodenum was more susceptible than the ileum to the antispasmodic action of amiodarone and again this effect was slow in onset and not reversible. The highest inhibition of ACh-induced contractions by amiodarone was obtained in guinea-pig stomach fundus. In these preparations treated with a low amiodarone concentration (20 microM) the response to ACh was restored after drug removal. In rat stomach fundus the effect of amiodarone was low and not reversible. Like amiodarone, Ca2+ lowering caused a decrease in the response to ACh with the following order of effectiveness: guinea-pig stomach greater than guinea-pig duodenum greater than guinea-pig ileum greater than rat stomach. The inhibitions caused by amiodarone and by low Ca2+ were always additive. These results indicate that amiodarone exerts an antispasmodic effect on the gastrointestinal tract and that regional and species differences exist for this action. The possible involvement of Ca2+ in this effect is discussed.
Gaion
R M
RM
Department of Pharmacology, University of Padova, Italy.
Basadonna
O
O
Santostasi
G
G
Fantin
M
M
Maragno
I
I
Dorigo
P
P
D000109:Acetylcholine / Q000494:pharmacology; D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004386:Duodenum / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects
D010276:Parasympatholytics; D000638:Amiodarone; D000109:Acetylcholine; D002118:Calcium