MECHANISMS OF RELAXING ACTION OF PAPAVERINE ON ISOLATED CANINE CORPUS CAVERNOSUM

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  • Yoshida Kazuhiro
    Department of Physiology I School of Medicine, Fukuoka University Department of Urology School of Medicine, Fukuoka University

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Other Title
  • 犬摘出陰茎海綿体におけるパパベリンの作用機序

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The mechanisms of relaxing effect of papaverine on the phenylephrine (10-6M)-or the high K+ (30mM)-induced contracture were studied on the isolated canine corpus cavernosum. Rod shaped preparation of the corpus cavernosum without the tunica albuginea was mounted in a tissue bath, immersed in Tyrode solution and the isometric tension was recorded. Cumulative applications of papaverine (10-6-3×10-5M) relaxed the phenylephrine (10-6M)- or the high K+ (30mM)-induced contracture with a dose-dependent manner. A pretreatment with papaverine (10-510-4M) dose-dependently reduced the magnitude of the phenylephrine (10-6M)-induced contracture, more prominently in the tonic than in the phasic component, while reduced that of the high K+ (30mM)-induced contracture in both components. The relaxing effect of papaverine (5×10-6M) on the high K+ (30mM)-induced contracture was antagonized by an increase in extracellular Ca++ concentration. A reintroduction of Ca++ after perfusion of Ca++ free and high K+ (30mM) solution containing 1mM EGTA failed to bring about normal contractile activity in the presence of papaverine (10-4M), Papaverine, even if its high concentration (10-4M), could not completely abolish the transient phasic contraction evoked norepinephrine (10-5M) which was abolished by ryanodine (3×10-6M), in Ca++ free solution. Isoproterenol (10-8-10-6M) or dibutyryl cyclic-AMP (10-5-10-3M) relaxed the phenylephrine (10-6M)- and the high K+ (30mM)-induced contracture. The relaxing effect of isoproterenol (10-8-10-6M) or dibytyryl cyclic-AMP (10-5-10-3M) on the phenylephrine (10-6M)- or the high K+ (30mM)-induced contracture was promoted by low concentration (10-6M) of papaverine. These results suggest that the mechanisms of relaxing action of papaverine on the isolated canine corpus cavernosum are an inhibition of the voltage-dependent and receptor-operated influx of Ca++, depression of Ca++ store sites and an increase in cellular cyclic-AMP level.

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