d'Emmanuele di Villa Bianca R, Sorrentino R, Roviezzo F, Imbimbo C, Palmieri A, De Dominicis G, Montorsi F, Cirino G, Mirone V
Dipartimento di Farmacologia Sperimentale, Università di Napoli-Federico II, Naples, Italy.
Int J Impot Res. 2005 Mar-Apr;17(2):127-33. doi: 10.1038/sj.ijir.3901293.
Apomorphine is used in the erectile dysfunction therapy and its action has been ascribed to the stimulation of central dopamine receptor. At the present stage, very little is known about the peripheral action of apomorphine on human corpus cavernosum (HCC). We have investigated the peripheral action of apomorphine and the role of dopamine receptors in HCC. We here demonstrate that both D1 and D2 receptors were expressed in the HCC, D1 receptors were two-fold more abundant than D2 and that both receptors were mainly localized on the smooth muscle cell component. Apomorphine in vitro exerted an anti-alpha1 adrenergic activity in human cavernosal strips since it prevented contraction induced by phenylephrine (PE), but not by U46619 or endothelin. Apomorphine elicited endothelium-independent and concentration-dependent relaxation of the strips contracted by PE, U46619 or endothelin. The EC50 values (microM) for apomorphine, in the presence and absence of endothelium, were 51.0+/-16 and 16.0+/-14, 120+/-19 and 150+/-18, 59.0+/-15 and 140+/-50 on PE-, U46619- or endothelin-induced contraction, respectively. Selective dopamine receptor agonist A-68930 (D1-like), but not quinpirole (D2-like), caused concentration-dependent relaxation of the cavernosal strips, which was partially prevented by endothelium removal or by treatment with an inhibitor of nitric oxide (NO) synthase. In conclusion, we show that (1) apomorphine has a peripheral relaxant direct effect as well as an antiadrenergic activity, (2) HCC possesses more D1-like (D1 and D5) than D2-like (D2, D3 and D4) receptors, (3) both D1- and D2-like receptors are mainly localized on smooth muscle cells and (4) the relaxant activity is most probably mediated by D1-like receptor partially through NO release from endothelium.
阿扑吗啡用于勃起功能障碍治疗，其作用归因于对中枢多巴胺受体的刺激。目前，关于阿扑吗啡对人阴茎海绵体（HCC）的外周作用知之甚少。我们研究了阿扑吗啡的外周作用以及多巴胺受体在HCC中的作用。我们在此证明，D1和D2受体均在HCC中表达，D1受体的丰度比D2受体高两倍，且两种受体主要定位于平滑肌细胞成分上。阿扑吗啡在体外对人阴茎海绵体条带具有抗α1肾上腺素能活性，因为它可阻止去氧肾上腺素（PE）诱导的收缩，但不能阻止U46619或内皮素诱导的收缩。阿扑吗啡可引起由PE、U46619或内皮素收缩的条带产生非内皮依赖性且浓度依赖性的舒张。在有内皮和无内皮的情况下，阿扑吗啡对PE、U46619或内皮素诱导收缩的EC50值（微摩尔）分别为51.0±16和16.0±14、120±19和150±18、59.0±15和140±50。选择性多巴胺受体激动剂A-68930（D1样）而非喹吡罗（D2样）可引起阴茎海绵体条带的浓度依赖性舒张，去除内皮或用一氧化氮（NO）合酶抑制剂处理可部分阻止这种舒张。总之，我们表明：（1）阿扑吗啡具有外周舒张直接作用以及抗肾上腺素能活性；（2）HCC中D1样（D1和D5）受体比D2样（D2、D3和D4）受体更多；（3）D1样和D2样受体均主要定位于平滑肌细胞上；（4）舒张活性很可能由D1样受体介导，部分通过内皮释放NO实现。
