M3 muscarinic receptor- and Ca influx-mediated muscle contractions induced by croton oil in isolated rabbit jejunum

Aim of study

Croton oil is the fruit oil of Croton tiglium L., which is well known in folk medicine for the treatment of gastrointestinal (GI) diseases, including constipation, abdominal pain, peptic ulcer, and intestinal inflammation for a long period. This study was to investigate the pharmacological effect of croton oil on GI tract.

Materials and methods

The effect of croton oil on the smooth muscle contractions was investigated in vitro using the isolated rabbit jejunum model.

Results

Croton oil has a biphasic action contracting and relaxing intestinal tissue. At the concentrations of 20–80 μg/mL, croton oil produced a concentration-dependent increase in the amplitude and tension of muscle contractions, whereas at high concentrations (>200 μg/mL) it decreased the contractile amplitude and had no impact on the tension. Moreover, croton oil was less effective in increasing muscle amplitude and tension than Ach, confirming that the effect of croton oil on muscle contractions is not a simply stimulatory or inhibitory action, but a unique modulatory process depending on the concentration of croton oil. In addition, croton oil concentration-dependently suppressed the frequency of muscle contractions. On the other hand, atropine (10 μM) and 4-DAMP (10 μM) produced a significant inhibition of contractions caused by croton oil, while either hexamethonium (10 μM) or methoctramine (10 μM) was inactive, implying that the regulatory effects of croton oil on GI motility are mediated via the activation of M3 muscarinic receptor. Furthermore, muscle contractions induced by croton oil were dramatically reduced by verapamil (0.1 μM) but not by NE (1 μM), suggesting that the action of croton oil on GI motility is also mediated by Ca²⁺ influx through L-type Ca²⁺ channel.

Conclusions

The results suggest that croton oil possesses spasmogenic and spasmolytic properties and the regulatory effects of croton oil on GI motility are mediated via the activation of M3 muscarinic receptor and Ca²⁺ influx through L-type Ca²⁺ channel.