Jpn. J. Pharmacol. 72 (2), 111-118 (1996)

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

Bo-Kyung Kim (#), Hiroshi Ozaki (*), Masatoshi Hori and Hideaki Karaki

Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Yayoi 1-1-1, Tokyo 113, Japan (#) Present address: Department of Veterinary Physiology, Animal Resources Research Center, Kon-Kuk University, Seong Dong-ku, Seoul 133-701, Korea (*) To whom correspondence should be addressed.

Abstract: 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.

Keywords: Uterine smooth muscle, Phorbol ester, Relaxation, Cytosolic Ca2+ level, Pregnancy

Copyright© The Japanese Pharmacological Society 1996

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