Kimoto Y, Kessler R, Constantinou C E
Division of Urology, Stanford University School of Medicine, California 94305.
J Urol. 1990 Dec;144(6):1497-9. doi: 10.1016/s0022-5347(17)39785-9.
The relaxation mechanism of the antispasmodics, papaverine and thiphenamil on isolated human corpus cavernosum (CC) was investigated. CC tissues were obtained from 12 impotent men undergoing surgery for insertion of penile prostheses. CC preparations were mounted in a tissue bath and the isometric tension was recorded. Papaverine and thiphenamil consistently inhibited high-potassium ([K])-induced contractions in a dose-dependent manner. Noradrenaline (NA)-induced contractions were inhibited by both agents in a non-competitive manner. The pD'2 values were 4.77 +/- 0.20 for papaverine and 4.58 +/- 0.13 for thiphenamil. Papaverine at 10(-4) M, the concentration at which high-[K]-induced contraction was abolished, suppressed NA-induced contraction by approximately 85%. In the Ca2(+)-free solution containing two mM EGTA, NA-induced contraction was suppressed by approximately 90%. This contraction was inhibited by papaverine or thiphenamil in a dose-dependent manner and was abolished by papaverine at 10(-4). These results suggest that papaverine and thiphenamil relax CC tissue by the inhibition of extracellular Ca2+ influx (mainly voltage-dependent Ca2+ influx) and by the inhibition of release and/or storage of intracellular stored Ca2+.
研究了解痉药罂粟碱和替芬那米对离体人海绵体（CC）的舒张机制。CC组织取自12名接受阴茎假体植入手术的阳痿男性。将CC制剂安装在组织浴中并记录等长张力。罂粟碱和替芬那米以剂量依赖性方式持续抑制高钾（[K]）诱导的收缩。两种药物均以非竞争性方式抑制去甲肾上腺素（NA）诱导的收缩。罂粟碱的pD'2值为4.77±0.20，替芬那米的pD'2值为4.58±0.13。10^(-4)M的罂粟碱（即高钾诱导收缩被消除时的浓度）可使NA诱导的收缩抑制约85%。在含有2 mM EGTA的无钙溶液中，NA诱导的收缩被抑制约90%。这种收缩被罂粟碱或替芬那米以剂量依赖性方式抑制，并在10^(-4)时被罂粟碱消除。这些结果表明，罂粟碱和替芬那米通过抑制细胞外Ca2+内流（主要是电压依赖性Ca2+内流）以及抑制细胞内储存Ca2+的释放和/或储存来舒张CC组织。
