Mechanism of mesaconitine‐induced contractile response in guinea‐pig ileum

Mesaconitine (MA) caused contractions of the guinea‐pig isolated ileum in a dose‐dependent manner (10⁻⁸ −10⁻⁵ g ml⁻¹), slightly potentiated the contractile response to acetylcholine (ACh) and histamine and enhanced responses to electrical stimulation. Repeated application of MA (10⁻⁵ g ml⁻¹) produced tachyphylaxis. Atropine blocked contractions to MA (3 times 10⁻⁷ g ml⁻¹), but only partially those to MA (10⁻⁵ g ml⁻¹). Morphine, strychnine and hemicholinium‐3, but not hexamethonium, also inhibited MA‐induced contractions. Contractions produced by both doses of MA were abolished by cocaine, tetrodotoxin, or noradrenaline, or by previous cooling of the ileum. The atropine‐resistant contractions produced by MA (10⁻⁵ g ml⁻¹) were blocked by indomethacin. MA (3 times 10⁻⁷ −10⁻⁵ g ml⁻¹) elicited a dose‐dependent release of ACh from the isolated ileum which was blocked by treatment with tetrodotoxin or cocaine, or exclusion of calcium ions from the bath. It is concluded that the contractions induced by lower doses of MA are brought about by the release of ACh from the postganglionic cholinergic nerve and that the contractions by higher doses could also be mediated by release of prostaglandins from the ileum. 1980 Royal Pharmaceutical Society of Great Britain