Abstract
An inhibitory effect of beauvericin, a cyclodepsipeptide, on a high K+-induced contraction in guinea-pig taenia coli was compared with those of verapamil, an organic Ca2+ antagonist, and monensin, an inhibitor of mitochondrial respiration. Beauvericin (10-5 M), verapamil (5×10-7 M) or monensin (10-6 M) markedly inhibited the tonic contraction, while these drugs showed less effect on the phasic contraction. Beauvericin at a lower concentration (10-6 M) competitively inhibited the Ca2+-induced contraction in depolarized muscle, whereas higher concentrations (3×10-6 or 10-5 M) non-competitively inhibited this contraction. Verapamil (10-8-5×10-7 M) competitively inhibited and monensin at a low concentration (10-7 M) non-competitively inhibited this contraction. A contraction induced by 0.5 mM Ca2+ was inhibited by beauvericin with an IC50 (concentration needed for 50% inhibition) of 2.8×10-7 M, verapamil with an IC50 of 2.9×10-8 M, and nifedipine with an IC50 of 1.8×10-9 M. 10-6 M CGP 28392, a Ca2+ channel facilitator, increased the IC50 of beauvericin, verapamil or nifedipine. Although the inhibitory effect of monensin (10-7-10-6 M) on the high K+-induced contraction was reduced under hypoxia, the effects of beauvericin (10-7-10 -5 M) and verapamil (10-8-10-7 M) were not modified. Beauvericin (10-5 M) changed neither the intracellular Na+ and K+ contents of the depolarized muscle nor the Ca2+-induced contraction in the chemically skinned taenia coll. These results suggest that the inhibitory action of beauvericin (10-5 M) on the high K+-induced tonic contraction is due to the non-competitive inhibition of Ca2+ entry through the voltage-dependent Ca2+ channel of the intestinal smooth muscle cell.
