Nakajyo S, Matsuoka K, Kitayama T, Yamamura Y, Shimizu K, Kimura M, Urakawa N
Department of Veterinary Pharmacology, Nippon Veterinary and Zootechnical College, Tokyo, Japan.
Jpn J Pharmacol. 1987 Nov;45(3):317-25. doi: 10.1254/jjp.45.317.
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)
将环缩肽白僵菌素对豚鼠结肠带高钾诱导收缩的抑制作用，与有机钙拮抗剂维拉帕米和线粒体呼吸抑制剂莫能菌素的抑制作用进行了比较。白僵菌素（10⁻⁵ M）、维拉帕米（5×10⁻⁷ M）或莫能菌素（10⁻⁶ M）显著抑制强直收缩，而这些药物对相性收缩的作用较小。较低浓度（10⁻⁶ M）的白僵菌素竞争性抑制去极化肌肉中钙诱导的收缩，而较高浓度（3×10⁻⁶或10⁻⁵ M）则非竞争性抑制这种收缩。维拉帕米（10⁻⁸ - 5×10⁻⁷ M）竞争性抑制，低浓度（10⁻⁷ M）的莫能菌素非竞争性抑制这种收缩。0.5 mM钙诱导的收缩被白僵菌素抑制，IC50（50%抑制所需浓度）为2.8×10⁻⁷ M，维拉帕米的IC50为2.9×10⁻⁸ M，硝苯地平的IC50为1.8×10⁻⁹ M。10⁻⁶ M的钙通道促进剂CGP 28392增加了白僵菌素、维拉帕米或硝苯地平的IC50。尽管在缺氧条件下莫能菌素（10⁻⁷ - 10⁻⁶ M）对高钾诱导收缩的抑制作用减弱，但白僵菌素（10⁻⁷ - 10⁻⁵ M）和维拉帕米（10⁻⁸ - 10⁻⁷ M）的作用未改变。白僵菌素（10⁻⁵ M）既不改变去极化肌肉的细胞内钠和钾含量，也不改变化学去表皮结肠带中钙诱导的收缩。（摘要截短于250字）
