L-Cysteine and Sodium Hydrosulphide Inhibit Spontaneous Contractility in Isolated Pregnant Rat Uterine Strips in vitro

Abstract

The control of myometrial contractility during pregnancy and parturition is not fully understood. Gas signalling molecules, such as nitric oxide and carbon monoxide, have been shown to relax the myometrium and may be involved in the control of contractility. Hydrogen sulphide has recently been shown to be produced endogenously in animal and human tissue and to have a signalling function. The aim of the study was to investigate the effect of L-cysteine and sodium hydrosulphide, potential hydrogen sulphide donors, on pregnant rat uterine contractility in vitro. Strips of pregnant rat uterus (n=22) were set up in a standard organ bath system. Following equilibration and recording of spontaneous contractility, the tissue was exposed to 45 mM potassium chloride followed by 1 nM oxytocin. Dose ranges of 10(-8) - 10(-3) M of L-cysteine (n=8) or sodium hydrosulphide (n=8) were subsequently applied to the tissue. In a third series of experiments (n=6) the effect of doses of 10(-9), 10(-6) and 10(-3) M of L-cysteine, D-cysteine, L-serine, DL-methionine and DL-homocysteine on myometrial contractility were compared. Contractions were integrated over 10 min. periods and the values were compared by one-way analysis of variance. L-Cysteine and sodium hydrosulphide produced significant dose-dependent decreases in uterine spontaneous contractility. Of the amino acids tested, only L-cysteine produced a significant reduction in spontaneous contractility at a dose of 10(-3) M. This study has demonstrated novel tocolytic actions of L-cysteine and sodium hydrosulphide, however further work is required to determine their mechanisms of action.

A New Slow Releasing, H2S Generating Compound, GYY4137 Relaxes Spontaneous and Oxytocin-Stimulated Contractions of Human and Rat Pregnant Myometrium

“…Notwithstanding these experimental conditions clear effects of GYY4137 are apparent. Consistent with previous work [6], [29] we found that NaHS decreased or even abolished spontaneous contractility in rat and human myometrium.…”

“…Hydrogen sulphide (H 2 S) is a gaseous signalling molecule that has been implicated in several physiological and pathophysiological processes from long term potentiation [1] and inflammation [2], to smooth muscle contractility [3], [4], [5], [6]. Two cytosolic enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) [7] act on the sulphur containing amino acids, cysteine and homo-cysteine, to produce H 2 S [8], [9].…”

“…Thus an endogenous molecule that can reduce contractility is of interest. It has already been shown that the uterus possesses the enzymes to produce H 2 S from L-cysteine, and reports have shown H 2 S to be able to reduce contractions of myometrium from rat and human [6], [29], [30]. Thus alterations of H 2 S levels may be an attractive target for therapeutic manipulation in problematic labours.…”

Expression of Cystathionine β-synthase and Cystathionine γ-lyase in Human Pregnant Myometrium and Their Roles in the Control of Uterine Contractility

“…Sidhu et al[21] previously showed that L-cysteine causes decreases in amplitude and frequency of spontaneous contractions of pregnant rat uterine strips in vitro , however, they did not show which H 2 S synthetic enzyme is involved in the action of L-cysteine. The present study demonstrated that endogenous H 2 S has dual effects on the contractility of human myomentrium as showing that L-cysteine dose-dependently inhibited spontaneous contraction amplitude in the concentration range of 10 −7 –10 −2 mol/L, whereas it induced tonic contraction and increased the frequency of spontaneous contractions at high concentration (10 −3 mol/L).…”

“…In another hand, it has also been shown to enhance the vascular tension [19] and provoke tachykinin-mediated bronchoconstriction [20]. Sidhu et al [21] recently reported that H 2 S inhibits spontaneous contractility of rat uterine strip in vitro . To date, there are no studies examining the roles of endogenous-produced H 2 S in regulating the contractility of human uterine smooth muscle in particular, during pregnancy and labour.…”