Further evidence of endogenous hydrogen sulphide as a mediator of relaxation in human and rat bladder

Abstract

We investigated the expression of hydrogen sulphide (H 2 S) in human and rat lower urinary tract (including bladder, prostate and urethra) tissues, and we sought to determine whether H 2 S induces relaxation of human and Sprague-Dawley (SD) rat bladder strips. Human normal lower urinary tract tissue was obtained for the evaluation of endogenous H 2 S productivity using a sulphide-sensitive electrode and for the analysis of the expression levels of all three synthases of endogenous H 2 S, cystathionine b-synthase (CBS), cystathionine c lyase (CSE) and 3-mercaptopyruvate sulphur transferase (MPST, as known as 3-MST) by Western blot assay. CBS, CSE and MPST were located in human sample slides by immunohistochemistry. Human and male adult SD rat bladder strips were tested for H 2 S function with a transducer and recorded. All experiments were repeated six times. The endogenous H 2 S productivity and the H 2 S synthases had various distributions in the human and rat lower urinary tract tissues and were located in both epithelial and stromal sections. L-cysteine (L-Cys, a substrate of CBS, CSE and MPST) elicited relaxation in a dose-dependent manner on human bladder strips pre-contracted by acetylcholine chloride. This effect could be diminished by the ATP-sensitive potassium ion (K ATP ) channel blocker glibenclamide (GLB), the CSE inhibitor DL-propargylglycine (PPG) and the CBS inhibitor hydroxylamine (HA). H 2 S and its three synthases were present in the human and rat lower urinary tract tissues and relaxed human and rat bladder strips, which implied that endogenous H 2 S might play a role in physiological function and pathological disorders of the lower urinary tract symptoms (LUTS) or overactive bladder (OAB).

Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

“…Since H 2 S and its synthases are present in the lower urinary tract tissues of various species, it is believed that endogenous H 2 S might play a role in the physiological function of the bladder and/or in pathological conditions such as overactive bladder (11). It has been suggested that in DSM, H 2 S induces concentrationdependent contraction by stimulating tachykinins release and activation of NK 1 and NK 2 receptors (37).…”

Hydrogen Sulfide and Urogenital Tract

“…The presence of H 2 S pathway has been also confirmed by using biopsy from cancer-free human prostate (Gai et al 2013). Moreover, Guo and coworkers have demonstrated that both cell activity and CBS/CSE protein levels are higher in the androgen-dependent prostate cancer cell LNCaP than in all the other cell lines evaluated and that dihydrotestosterone downregulates this activity.…”

“…CSE and CBS were detected by immunohistochemistry in nerve fibers and are widely distributed within the smooth muscle layer of the pig bladder neck (Fernandes et al 2013a). CBS, CSE, and 3MST have been also shown to be present in rat bladder (Gai et al 2013). In mouse bladder, only the presence of CSE has been reported so far, (Matsunami et al 2012).…”

“…The overactive bladder syndrome, which may be due to involuntary contractions of the smooth muscle of the bladder (detrusor) during the storage phase, is a common problem (Milsom et al 2001). H 2 S has been shown to be involved in the bladder function in different species such as trout, rat, pig, and human (Fusco et al 2012;Gai et al 2013;Fernandes et al 2013a, b;Patacchini et al 2004;Dombkowski et al 2006). …”

“…Similarly, to human tissues, homogenates of bladder can generate detectable amount of H 2 S in basal or stimulated conditions (Dombkowski et al 2006;Matsunami et al 2012;Gai et al 2013). The expression of the enzymes responsible of H 2 S production has been reported in bladder of rat, pig, and mice by using different methods.…”