Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation.
Hydrogen sulfide (H(2)S) 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 H(2)S. Human penile tissue possesses both CBS and CSE, and tissue homogenates efficiently convert L-Cys to H(2)S. 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 H(2)S [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/H(2)S pathway mediates human corpus cavernosum smooth-muscle relaxation.
d'Emmanuele di Villa Bianca
Roberta
R
Department of Experimental Pharmacology, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy.
Sorrentino
Raffaella
R
Maffia
Pasquale
P
Mirone
Vincenzo
V
Imbimbo
Ciro
C
Fusco
Ferdinando
F
De Palma
Raffaele
R
Ignarro
Louis J
LJ
Cirino
Giuseppe
G
D000818:Animals; D003545:Cysteine / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000502:physiology*; D051381:Rats
D003545:Cysteine; D006862:Hydrogen Sulfide