Kim B K, Ozaki H, Hori M, Karaki H
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan.
Jpn J Pharmacol. 1996 Oct;72(2):111-8. doi: 10.1254/jjp.72.111.
Activation of voltage-dependent Ca2+ channels by high K+ (40 mM) increased the cytosolic Ca2+ level ([Ca2+]i) (estimated by fura-PE3 fluorescence ratio) and force in myometrium isolated from pregnant (21 days after gestation) and non-pregnant (estrus) rats. 12-Deoxyphorbol 13-isobutyrate (DPB, 1 mM) decreased the high (K+)-stimulated [Ca2+]i and force in a concentration-dependent manner. The inhibitory effect was stronger in the pregnant myometrium than in the non-pregnant myometrium. In the pregnant myometrium, the increase in Ca2+ permeability by ionomycin (1 microM) greatly increased [Ca2+]i and force, which were only partially inhibited by verapamil (10 microM). DPB (1 microM) inhibited the verapamil-insensitive component of the increases in [Ca2+]i and muscle tension. Oxytocin (100 nM) and thapsigargin (1 microM) also induced a verapamil-insensitive increase in [Ca2+]i and force, and DPB (1 microM) inhibited these increments. Ca2+ sensitivity of contractile elements, estimated from the relationships between Ca2+ and muscle force in intact and alpha-toxin permeabilized muscle, was not significantly changed by DPB (1 microM). In summary, DPB inhibits the increase in [Ca2+]i more strongly in myometrium isolated from pregnant rats than that from non-pregnant rats without any change in the [Ca2+]i/tension relationship. Since DPB decreased [Ca2+]i-rise induced by three different mechanisms, DPB may activate Ca2+ extrusion, rather than to inhibit a specific influx pathway, to decrease [Ca2+]i.
高钾（40 mM）激活电压依赖性Ca2+通道可增加从妊娠（妊娠21天）和非妊娠（发情期）大鼠分离的子宫肌层中的胞质Ca2+水平（[Ca2+]i）（通过fura-PE3荧光比率估算）和张力。12-脱氧佛波醇13-异丁酸酯（DPB，1 mM）以浓度依赖性方式降低高钾（K+）刺激的[Ca2+]i和张力。抑制作用在妊娠子宫肌层中比在非妊娠子宫肌层中更强。在妊娠子宫肌层中，离子霉素（1 microM）增加Ca2+通透性可极大地增加[Ca2+]i和张力，而维拉帕米（10 microM）仅部分抑制它们。DPB（1 microM）抑制[Ca2+]i和肌肉张力增加中对维拉帕米不敏感的成分。催产素（100 nM）和毒胡萝卜素（1 microM）也诱导对维拉帕米不敏感的[Ca2+]i和张力增加，而DPB（1 microM）抑制这些增加。从完整和α-毒素通透的肌肉中Ca2+与肌肉张力的关系估算的收缩元件的Ca2+敏感性，未因DPB（1 microM）而发生显著变化。总之，DPB在从妊娠大鼠分离的子宫肌层中比从非妊娠大鼠分离的子宫肌层中更强烈地抑制[Ca2+]i的增加，而[Ca2+]i/张力关系无任何变化。由于DPB降低了由三种不同机制诱导的[Ca2+]i升高，DPB可能激活Ca2+外流，而非抑制特定的内流途径，以降低[Ca2+]i。
