Mechanism of Relaxant Response to Papaverine on the Smooth Muscle of Non-pregnant Rat Uterus

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In the present paper, We examined a mechanism of the papaverine-induced relaxation in the smooth muscle of non-pregnant rat uterus. The hyperosmotic 65 mM KCl(H-65K^+)-or oxytocin-induced contraction in the uterus was inhibited by an addition of papaverine in a concentration-dependent manner. Papaverine did not increase both cAMP and cGMP contents in the uterus in the presence of H-65K^+ or oxytocin. In fura 2 loaded muscles, papaverine did not affect an increase of[Ca^<2+>]_i level by high K^+ or oxytocin. In permeabilized muscles, papaverine had no effect on the Ca^<2+>-induced contraction. H-65K^+ and oxytocin increased the rate of oxygen consumption 1.8 and 1.5 times higher than that in the resting condition, respectively. The increase of oxygen consumption in the H-65K^+ or oxytocin was significantly inhibited by papaverine(1-100μM). These results suggested that papaverine inhibits smooth muscle contraction mainly by inhibition of mitochondrial respiration in rat uterus as well as guinea pig ileum, which shows a highly spontaneous activity and a highly metabolic dependency of a contraction.
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