Increased Inhibitory Effect of Phorbol Ester on Cytosolic Ca2+ Level and Contraction in Rat Myometrium after Gestation

摘要

References(28) Cited-By(10) Activation of voltage-dependent Ca2+ channels by high K+ (40 mM) increased the cyiosolic 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 μM) greatly increased [Ca2+]i and force, which were only partially inhibited by verapamil (10 μM). DPB (1 μM) inhibited the verapamil-insensitive component of the increases in [Ca2+]i and muscle tension. Oxyiocin (100 nM) and thapsigargin (1 μM) also induced a verapamil-insensitive increase in [Ca2+]i and force, and DPB (1 μM) inhibited these increments. Ca2+ sensitivity of contractile elements, estimated from the relationships between Ca2+ and muscle force in intact and α-toxin permeabilized muscle, was not significantly changed by DPB (1 μM). 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.