Jin Liming, Teixeira Cleber E, Webb R Clinton, Leite Romulo
Department of Internal Medicine, Division of Endocrinology, Clinical Nutrition and Vascular Medicine, University of California, Davis, CA 95616, United States.
Eur J Pharmacol. 2008 Aug 20;590(1-3):363-8. doi: 10.1016/j.ejphar.2008.06.001. Epub 2008 Jun 7.
Protein kinase C (PKC) is involved in the regulation of vascular smooth muscle contraction. However, the role of PKC in erectile function is poorly understood. This study investigated whether PKC mediates agonist-induced contractions in mouse penile tissue (corpora cavernosa). We also compared the effects of PKC activators and inhibitors on contractile responses in mouse corpus cavernosum with those in mouse aorta. Aortic rings and corpus cavernosal strips from C57BL/6J mice were mounted in the organ bath for isometric tension recording. Our data showed that a PKC(alpha/beta) selective inhibitor, G(ö)6976 (10 microM), inhibited phenylephrine and 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F(2alpha) (U46619, a thromboxane mimetic)-induced contractions in mouse aorta, reducing the maximum contraction by 94% and 17%, respectively. A non-selective PKC inhibitor, chelerythrine (30 microM), also significantly reduced phenylephrine- and U46619-induced maximum contractions in mouse aorta. However, G(ö)6976 and chelerythrine had no significant effects on phenylephrine- and U46619-induced contractions in corpus cavernosum. Furthermore, a PKC activator, phorbol-12,13-dibutyrate (0.1 microM), significantly increased contractions in aorta (208+/-14% of KCl-induced maximum contraction) but failed to cause contractions in corpus cavernosum at 1 and 10 microM. Western blot analysis data suggested that protein expression of PKC was similar in aorta and corpus cavernosum. Taken together, our data indicate that PKC does not have a significant role in agonist-induced contractions in mouse corpus cavernosum, whereas it mediates the contractile response to agonists in the aorta.
蛋白激酶C（PKC）参与血管平滑肌收缩的调节。然而，PKC在勃起功能中的作用尚不清楚。本研究调查了PKC是否介导激动剂诱导的小鼠阴茎组织（海绵体）收缩。我们还比较了PKC激活剂和抑制剂对小鼠海绵体与小鼠主动脉收缩反应的影响。将C57BL/6J小鼠的主动脉环和海绵体条安装在器官浴中进行等长张力记录。我们的数据表明，一种PKC（α/β）选择性抑制剂Gö6976（10微摩尔）抑制苯肾上腺素和9,11-二脱氧-11α,9α-环氧甲烯前列腺素F2α（U46619，一种血栓素类似物）诱导的小鼠主动脉收缩，分别将最大收缩降低94%和17%。一种非选择性PKC抑制剂白屈菜红碱（30微摩尔）也显著降低苯肾上腺素和U46619诱导的小鼠主动脉最大收缩。然而，Gö6976和白屈菜红碱对苯肾上腺素和U46619诱导的海绵体收缩没有显著影响。此外，一种PKC激活剂佛波醇-12,13-二丁酸酯（0.1微摩尔）显著增加主动脉收缩（为氯化钾诱导的最大收缩的208±14%），但在1和10微摩尔时未能引起海绵体收缩。蛋白质印迹分析数据表明，PKC的蛋白表达在主动脉和海绵体中相似。综上所述，我们的数据表明，PKC在激动剂诱导的小鼠海绵体收缩中没有显著作用，而它介导主动脉对激动剂的收缩反应。
