Mechanisms of relaxing action of papaverine on isolated canine corpus cavernosum

Abstract

The mechanisms of relaxing effect of papaverine on the phenylephrine (10(-6) M)- or the high K+ (30 mM)-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) approximately 3 x 10(-5) M) relaxed the phenylephrine (10(-6) M)- or the high K+ (30 mM)-induced contracture with a dose-dependent manner. A pretreatment with papaverine (10(-5) approximately 10(-4) M) dose-dependently reduced the magnitude of the phenylephrine (10(-6) M)-induced contracture, more prominently in the tonic than in the phasic component, while reduced that of the high K+ (30 mM)-induced contracture in both components. The relaxing effect of papaverine (5 x 10(-6) M) on the high K+ (30 mM)-induced contracture was antagonized by an increase in extracellular Ca++ concentration. A reintroduction of Ca++ after perfusion of Ca++ free and high K+ (30 mM) solution containing 1 mM EGTA failed to bring about normal contractile activity in the presence of papaverine (10(-4) M), Papaverine, even if its high concentration (10(-4) M), could not completely abolish the transient phasic contraction evoked norepinephrine (10(-5) M) which was abolished by ryanodine (3 x 10(-6) M), in Ca++ free solution. Isoproterenol (10(-8) approximately 10(-6) M) or dibutyryl cyclic-AMP (10(-5) approximately 10(-3) M) relaxed the phenylephrine (10(-6) M)- and the high K+ (30 mM)-induced contracture.(ABSTRACT TRUNCATED AT 250 WORDS)