title: Characterization of relaxant mechanism of H2 S in mouse corpus cavernosum.
abstract: The aim of this study was to investigate the mechanism of H2 S-induced relaxation in mouse corpus cavernosal tissue. l-cysteine (10(-6) × 10(-3) mol/L) and exogenous H2 S (NaHS; 10(-6) to 10(-3) mol/L) induced concentration-dependent relaxation. l-cysteine-induced relaxations was reduced by d,l-propargylglycine, a cystathionine gamma lyase (CSE) inhibitor but not influenced by aminooxyacetic acid, a cystathionine beta synthase (CBS) inhibitor. l-cysteine induced relaxations, but not of those of H2 S diminished in endothelium-denuded tissues. N(ω) -nitro-l-arginine (l-NA; 10(-4) mol/L), a nitric oxide synthase inhibitor, and ODQ (10(-4) mol/L), a guanylyl cyclase inhibitor, increased the H2 S-induced relaxation. Zaprinast (5 × 10(-6) mol/L) and sildenafil (10(-6) mol/L), phosphodiesterase inhibitors, inhibited H2 S-induced relaxation. Adenylyl cyclase inhibitors N-ethylmaleimide (2.5 × 10(-5) mol/L) and SQ22536 (10(-4) mol/L) reduced relaxation to H2 S. Also, H2 S-induced relaxation was reduced by KCl (50 mmol/L), 4-aminopyridine (10(-3) mol/L), a Kv inhibitor, glibenclamide (10(-5) mol/L), a KATP inhibitor or barium chloride (10(-5) mol/L), a KIR inhibitor. However, H2 S-induced relaxation was not influenced by apamin (10(-6) mol/L), a SKC a (2+) inhibitor, charybdotoxin (10(-7) mol/L), an IKC a (2+) and BKC a (2+) inhibitor or combination of apamin and charybdotoxin. Nifedipine (10(-6) mol/L), an L-type calcium channel blocker and atropine (10(-6) mol/L), a muscarinic receptor blocker, inhibited H2 S-induced relaxation. However, H2 S-induced relaxation was not influenced by ouabain (10(-4) mol/L), a Na(+) /K(+) -ATPase inhibitor. This study suggests that H2 S endogenously synthesizes from l-cysteine by CSE endothelium-dependent in mouse corpus cavernosum tissue, and exogenous H2 S may cause endothelium-independent relaxations via activation of K channels (KATP channel, KV channels, KIR channels), L-type voltage-gated Ca(2+) channels, adenylyl cyclase/cAMP pathway and muscarinic receptor, and there is the interaction between H2 S and NO/cGMP.
authors: Department of Pharmacology, Pharmacy Faculty, Çukurova University, Adana, Turkey.
authors: Fatma
authors: F
authors: Aydinoglu
authors: Department of Pharmacology, Medical Faculty, Çukurova University, Adana, Turkey.
authors: Nuran
authors: N
authors: Ogulener
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D010413:Penis / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D009569:Nitric Oxide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D003545:Cysteine; D006862:Hydrogen Sulfide
keywords: KCl channel blockers; aminooxyacetic acid; cAMP/GMP; d,l-propargylglycine; endothelium; hydrogen sulfide; l-cysteine; mouse corpus cavernosum