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花生四烯酸/环氧化酶级联、磷酸二酯酶 IV 和 Rho 激酶在 HS 诱导的小鼠海绵体平滑肌松弛中的作用。

The role of arachidonic acid/cyclooxygenase cascade, phosphodiesterase IV and Rho-kinase in HS-induced relaxation in the mouse corpus cavernosum.

机构信息

Department of Pharmacology, Pharmacy Faculty, Cukurova University, Adana, Turkey.

Department of Pharmacology, Medical Faculty, Cukurova University, Adana, Turkey.

出版信息

Pharmacol Rep. 2017 Aug;69(4):610-615. doi: 10.1016/j.pharep.2017.02.018. Epub 2017 Feb 24.

DOI:10.1016/j.pharep.2017.02.018
PMID:28501682
Abstract

BACKGROUND

Penile corpus cavernosum is an extremely vascularized tissue and cavernosal smooth muscle tone is regulated by the balance between contractile and relaxant factor. We investigated the possible role of arachidonic acid/cyclooxygenase cascade, phosphodiesterase IV (PDEIV) and Rho-kinase in exogenous hydrogen sulfide (HS)-induced relaxation in mouse corpus cavernosum.

METHODS

The relaxant response to HS (NaHS as exogenous HS; 1-1000μM) were obtained in isolated mouse corpus cavernosum tissues which pre-contracted by phenylephrine (5μM). The effects of 4-(4-octadecylphenyl)-4-oxobutenoic acid (OBAA; 10μM), a selective phospholipase A (PLA) inhibitor, indomethacin (1μM), a non-selective cyclooxygenase (COX) inhibitor, baicalein (10μM), a lipoxygenase (LOX) inhibitor, and proadifen (10μM), cytochrome P450 inhibitor, on the relaxant responses to HS were investigated. Furthermore, the effects of theophylline (500μM) and rolipram (1μM), a non-selective and selective PDEIV inhibitor, and fasudil (3μM), a specific Rho-kinase inhibitor, were studied on HS-induced relaxation.

RESULTS

HS-induced relaxations were significantly reduced by OBAA, indomethacin and proadifen but not baicalein. Furthermore, theophylline, rolipram and fasudil reduced HS-induced relaxations.

CONCLUSION

These results suggest that PLA, COX, cytochrome P450, PDEIV and Rho-kinase pathway may involve in HS-induced relaxation in mouse corpus cavernosum tissues.

摘要

背景

阴茎海绵体是一种极其富含血管的组织,海绵体平滑肌张力受收缩和舒张因子之间的平衡调节。我们研究了花生四烯酸/环氧化酶级联、磷酸二酯酶 IV(PDEIV)和 Rho-激酶在小鼠海绵体组织中诱导外源性硫化氢(HS)松弛中的可能作用。

方法

在预先用苯肾上腺素(5μM)收缩的分离小鼠海绵体组织中获得 HS(NaHS 作为外源性 HS;1-1000μM)的舒张反应。研究了 4-(4-十八烷基苯基)-4-氧代丁烯酸(OBAA;10μM)、一种选择性磷脂酶 A(PLA)抑制剂、吲哚美辛(1μM)、一种非选择性环氧化酶(COX)抑制剂、黄芩素(10μM)、一种脂氧合酶(LOX)抑制剂和 proadifen(10μM)、细胞色素 P450 抑制剂对 HS 舒张反应的影响。此外,还研究了茶碱(500μM)和 rolipram(1μM)、一种非选择性和选择性 PDEIV 抑制剂以及 fasudil(3μM)、一种特异性 Rho-激酶抑制剂对 HS 诱导松弛的影响。

结果

OBAA、吲哚美辛和 proadifen 显著降低 HS 诱导的松弛,但黄芩素没有。此外,茶碱、rolipram 和 fasudil 降低了 HS 诱导的松弛。

结论

这些结果表明 PLA、COX、细胞色素 P450、PDEIV 和 Rho-激酶途径可能参与了小鼠海绵体组织中 HS 诱导的松弛。

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