l-Cys/CSE/H2S pathway modulates mouse uterus motility and sildenafil effect
Emma Mitidieri1, Teresa Tramontano1, Erminia Donnarumma1
1Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, Naples, 80131, Italy.
Pharmacological Research
|June 22, 2016
Summary
Sildenafil enhances hydrogen sulfide (H2S) production in the mouse uterus, reducing uterine contractility. This effect, mediated by l-cysteine/cystathionine-γ-lyase (CSE)/H2S signaling, suggests new therapeutic avenues for uterine disorders.
Area of Science:
- Pharmacology
- Physiology
- Biochemistry
Background:
- Sildenafil, a PDE5 inhibitor, relaxes smooth muscle via H2S signaling.
- Sildenafil's mechanism in uterine relaxation remains unclear.
- H2S is produced from l-cysteine by CBS and CSE enzymes.
Purpose of the Study:
- Investigate H2S involvement in sildenafil-induced uterine contractility in mice.
- Elucidate the role of CBS and CSE in mediating sildenafil's effects on uterine motility.
Main Methods:
- Assessed CBS and CSE expression and activity in mouse uterus.
- Measured H2S production following sildenafil administration.
- Evaluated effects of sildenafil, l-cysteine, and H2S on uterine contractility.
- Utilized CSE knockout (CSE-/-) mice for mechanistic studies.
- Quantified cyclic guanosine monophosphate (cGMP) levels.
Main Results:
- Both CBS and CSE were expressed and functional in the mouse uterus.
- Sildenafil significantly increased uterine H2S production, blocked by CBS/CSE inhibition.
- Sildenafil, l-cysteine, and H2S reduced spontaneous uterine contractions.
- CSE inhibition and CSE-/- mice significantly attenuated sildenafil's effects.
- Sildenafil increased uterine cGMP levels, which was reduced by CSE inhibition.
Conclusions:
- L-cysteine/CSE/H2S signaling pathway modulates mouse uterine motility.
- Sildenafil exerts its uterine effects through this H2S-mediated pathway.
- Findings suggest potential therapeutic strategies for abnormal uterine contractility disorders.
