Medina P, Segarra G, Torondel B, Chuan P, Domenech C, Vila J M, Lluch S
Department of Physiology, University of Valencia, 46010, Valencia, Spain.
Br J Pharmacol. 2000 Nov;131(5):871-4. doi: 10.1038/sj.bjp.0703657.
Sildenafil (0.1 - 30 microM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1 - 100 microM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1 - 100 microM) had no effect on neurogenic contractions. The inhibition induced by sildenafil was not modified by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 - 30 microM) but it was abolished by the K(+) channel blockers tetraethylammonium (TEA, 1 mM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM). Sildenafil, zaprinast and SNP did not affect the contractions induced by noradrenaline. SNP (10 microM) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10 microM) and zaprinast (100 microM). ODQ (10 microM) inhibited the increase in cyclic GMP. Sildenafil inhibits adrenergic neurotransmission in human vas deferens. The inhibition is not related to accumulation of cyclic GMP but is probably due to activation of prejunctional large-conductance Ca(2+)-activated K(+) channels.
西地那非（0.1 - 30微摩尔），一种环磷酸鸟苷磷酸二酯酶5（PDE 5）抑制剂，可抑制34例输精管结扎术后人体输精管环段的电诱发收缩。另一种PDE 5抑制剂扎普司特（0.1 - 100微摩尔）以及一氧化氮（NO）供体硝普钠（SNP）（0.1 - 100微摩尔）对神经源性收缩无影响。西地那非诱导的抑制作用不受鸟苷酸环化酶抑制剂1H - [1,2,4]恶二唑并[4,3 - a]喹喔啉 - 1 - 酮（ODQ）（1 - 30微摩尔）的影响，但被钾离子通道阻滞剂四乙铵（TEA，1毫摩尔）、iberiotoxin（0.1微摩尔）和蝎毒素（0.1微摩尔）消除。西地那非、扎普司特和SNP不影响去甲肾上腺素诱导的收缩。SNP（10微摩尔）导致环磷酸鸟苷水平升高，西地那非（10微摩尔）和扎普司特（100微摩尔）可增强这种升高。ODQ（10微摩尔）抑制环磷酸鸟苷的增加。西地那非抑制人体输精管中的肾上腺素能神经传递。这种抑制与环磷酸鸟苷的积累无关，可能是由于突触前大电导钙激活钾通道的激活。
