Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation

被引:150
作者
Bianca, Roberta d'Emmanuele di Villa [2 ,3 ]
Sorrentino, Raffaella [2 ,3 ]
Maffia, Pasquale [2 ,4 ]
Mirone, Vincenzo [3 ]
Imbimbo, Ciro [3 ]
Fusco, Ferdinando [3 ]
De Palma, Raffaele [5 ]
Ignarro, Louis J. [1 ]
Cirino, Giuseppe [2 ,3 ]
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[2] Univ Naples Federico II, Dept Expt Pharmacol, I-80131 Naples, Italy
[3] Univ Naples Federico II, Interdept Res Ctr Sexual Med, I-80131 Naples, Italy
[4] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G40 NR, Lanark, Scotland
[5] Univ Naples 2, Dept Expt Med, I-80100 Naples, Italy
关键词
cystathionine beta-synthase (CBS); cystathionine gamma-lyase (CSE); H2S; penile erection; L-cysteine; CYSTATHIONINE GAMMA-LYASE; NITRIC-OXIDE SYNTHASE; ERECTILE FUNCTION; CARDIOVASCULAR-DISEASE; BETA-SYNTHASE; CYCLIC-GMP; IN-VITRO; MICE; DYSFUNCTION; INHIBITION;
D O I
10.1073/pnas.0807974105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hydrogen sulfide (H2S) is synthesized by 2 enzymes, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). L-Cysteine (L-Cys) acts as a natural substrate for the synthesis of H2S. Human penile tissue possesses both CBS and CSE, and tissue homogenates efficiently convert L-Cys to H2S. CBS and CSE are localized in the muscular trabeculae and the smooth-muscle component of the penile artery, whereas CSE but not CBS is also expressed in peripheral nerves. Exogenous H2S [sodium hydrogen sulfide (NaHS)] or L-Cys causes a concentration-dependent relaxation of strips of human corpus cavernosum. L-Cys relaxation is inhibited by the CBS inhibitor, aminoxyacetic acid (AOAA). Electrical field stimulation of human penile tissue, under resting conditions, causes an increase in tension that is significantly potentiated by either propargylglycine (PAG; CSE inhibitor) or AOAA. In rats, NaHS and L-Cys promote penile erection, and the response to L-Cys is blocked by PAG. Our data demonstrate that the L-Cys/H2S pathway mediates human corpus cavernosum smooth-muscle relaxation.
引用
收藏
页码:4513 / 4518
页数:6
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