Tsai_1991_Arch.Int.Pharmacodyn.Ther_310_116

The effects of berberine on the contractions of the longitudinal muscle of the guinea-pig isolated ileum were investigated. Lower concentrations of berberine (less than or equal to 5 x 10(-5) M) induced a parallel rightward shift of the dose-response curve of acetylcholine, suggesting that berberine is antagonizing the actions of acetylcholine at the receptors competitively. At higher concentration, berberine (1 x 10(-4) M) facilitated a rightward shift of the dose-response curve of acetylcholine with a reduction of maximum response, indicating that the interactions of the two agents changed from competitive to noncompetitive antagonism. The competitive antagonism is due to the actions of acetylcholine at the muscarinic receptors, while the noncompetitive antagonism is probably due to the action of berberine at other sites in addition to the muscarinic receptor sites. Berberine dose-dependently antagonized the effects of muscarine, a specific muscarinic receptor agonist, in a fashion similar to the antagonism of acetylcholine, providing evidence that the site of action of berberine is at the muscarinic receptors. Hexamethonium (7.5 x 10(-4) M) did not influence the effect of berberine on the concentration-response curve of acetylcholine and berberine had no effects on the contractions of the preparation elicited by histamine, suggesting its specificity for muscarinic receptors. Berberine also concentration-dependently reduced electrically induced cholinergic contractions, corresponding with its effects at the muscarinic receptor sites. Berberine had no effects on the contractions elicited by KCl, which acts at postreceptor sites. The action of berberine was reversible and dependent on the duration of incubation with the preparation; the longer the time of incubation with the tissues, the slower the recovery. The results of this series of experiments support the hypothesis that berberine blocks muscarinic receptors and this might be part of the explanation of its efficacy in the reduction of intestinal motility and in the treatment of diarrhea.