Simo decoction promotes contraction of antral circular smooth muscle mainly via muscarinic M3 receptor

Abstract

Ethnopharmacological relevance: Simo Decoction (SMD), a traditional Chinese medicine, included four elements, such as Fructus aurantii, Radix aucklandiae, Semen arecae and Radix linderae. It has been used to improve gastrointestinal dysmotility in clinical practice for a long history in China. However, the explicit mechanisms are unclear. The aim of this study was to investigate the effect of SMD on contractions of antral circular smooth muscle strips of Sprague-Dawley (SD) rats and its underlying mechanism.

Materials and methods: The antral circular strips were prepared in the organ bath under baseline or to be incubated with muscarinic receptor antagonist atropine (10(-6)M), muscarinic M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) (0.4×10(-6)M), muscarinic M2 receptor antagonist gallamine (10(-6)M), adrenergic receptor agonist adrenaline (10(-7)M), exogenous nitric oxide (NO) donor l-arginine (10(-4)M), nicotinic receptor antagonist hexamethonium chloride (10(-4)M) and Ca(2+) channel antagonist nifedipine (30nM), and consecutive concentrations of SMD were added to the bath to observe the strip responses. As a control, the responses of strips after administration with the same volume of Krebs solution as SMD were also noted. The strip responses to acetylcholine (10(-7)-10(-3)M) were also noted in organ bath to compare with SMD-induced contraction.

Results: SMD dose-dependently evoked hypercontractility of antral circular strips, and the maximal contractile effect of circular smooth muscle induced by SMD was significantly higher than that induced by acetylcholine (10(-3)M). The responses of antral circular strips to SMD were completely antagonized by atropine, 4-DAMP or 4-DAMP+gallamine, but partly inhibited by gallamine and partly suppressed by adrenaline, l-arginine, hexamethonium chloride and nifedipine.

Conclusions: SMD promotes contractions of antral circular strips in rats mainly via activation of muscarinic M3 receptor, but partly via activation of muscarinic M2 receptor, Ca(2+) channel and nicotinic receptor, inhibition of adrenergic receptor and releasing of NO.