monensin and beauvericin

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 x 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 x 10(-6) or 10(-5) M) non-competitively inhibited this contraction. Verapamil (10(-8)-5 x 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 x 10(-7) M, verapamil with an IC50 of 2.9 x 10(-8) M, and nifedipine with an IC50 of 1.8 x 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 coli.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Anti-Bacterial Agents; Calcium; Colon; Depsipeptides; Guinea Pigs; In Vitro Techniques; Male; Monensin; Muscle Contraction; Muscle Tonus; Muscle, Smooth; Peptides; Peptides, Cyclic; Potassium; Verapamil