Inhibitory effect of beauvericin on a high K+-induced tonic contraction in guinea-pig taenia coli.
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)
Nakajyo
S
S
Department of Veterinary Pharmacology, Nippon Veterinary and Zootechnical College, Tokyo, Japan.
Matsuoka
K
K
Kitayama
T
T
Yamamura
Y
Y
Shimizu
K
K
Kimura
M
M
Urakawa
N
N
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D003106:Colon / Q000187:drug effects; D047630:Depsipeptides; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008985:Monensin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010455:Peptides; D010456:Peptides, Cyclic / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D010455:Peptides; D010456:Peptides, Cyclic; C004456:beauvericin; D008985:Monensin; D014700:Verapamil; D011188:Potassium; D002118:Calcium