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内源性硫化氢在大鼠海绵体神经源性松弛中的作用。

Role of endogenous hydrogen sulfide in neurogenic relaxation of rat corpus cavernosum.

机构信息

Department of Medicine, UCL Medical School, University College London, UK.

出版信息

Biochem Pharmacol. 2012 May 1;83(9):1261-8. doi: 10.1016/j.bcp.2012.01.026. Epub 2012 Jan 28.

DOI:10.1016/j.bcp.2012.01.026
PMID:22306852
Abstract

Relaxation of corpus cavernosum during penile erection is mediated by a non-adrenergic non-cholinergic (NANC) neurotransmission and by the endothelium via the release of nitric oxide. Hydrogen sulfide (H(2)S) is an endogenous gaseous mediator which is a potent vasodilator and a neurotransmitter. This study was initiated to characterize the role of H(2)S in NANC neurogenic transmission in rat corpus cavernosum. The expression of H(2)S producing enzymes was assessed using RT-PCR as well as Western blotting and showed the expression of cystathionine γ-lyase (CSE) in rat corporal tissue. Homogenates from rat corpus cavernosum convert l-cysteine to H(2)S and this was partially inhibited by a CSE inhibitor, propargylglycine. Electrical stimulation of corporal tissue strips caused NANC relaxation. This neurogenic relaxation was significantly enhanced by inhibition of CSE by propargylglycine indicating that endogenously produced H(2)S may have a negative regulatory role in neurogenic relaxation of rat corpus cavernosum. To investigate this further we used physiologically relevant concentrations of exogenous NaHS, and showed that nanomolar concentrations could inhibit corporal relaxation induced by a nitroxyl (HNO) donor (Angeli's salt) but not with nitrosonium (NO(+)) or NO donors. This suggests that an interaction between endogenously produced H(2)S and nitroxyl (HNO) might be involved in erectile function.

摘要

阴茎勃起时,海绵体的松弛是由非肾上腺素能非胆碱能(NANC)神经传递和内皮细胞通过释放一氧化氮(NO)介导的。硫化氢(H2S)是一种内源性气体递质,具有很强的血管扩张作用和神经递质作用。本研究旨在探讨 H2S 在大鼠海绵体 NANC 神经传递中的作用。采用 RT-PCR 和 Western blot 检测 H2S 产生酶的表达,结果显示大鼠海绵体组织中胱硫醚γ-裂解酶(CSE)的表达。大鼠海绵体匀浆能将 L-半胱氨酸转化为 H2S,该反应被 CSE 抑制剂炔丙甘氨酸部分抑制。电刺激海绵体组织条可引起 NANC 松弛,炔丙甘氨酸抑制 CSE 可显著增强这种神经源性松弛,表明内源性产生的 H2S 可能对大鼠海绵体神经源性松弛具有负调控作用。为了进一步研究这一问题,我们使用了生理相关浓度的外源性 NaHS,结果表明纳摩尔浓度的 H2S 可以抑制硝基亚硝胺(Angeli's salt)诱导的海绵体松弛,但不能抑制亚硝酰阳离子(NO+)或其他 NO 供体诱导的松弛。这提示内源性 H2S 与硝基亚硝胺(HNO)之间可能存在相互作用,参与勃起功能。

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