In:
British Journal of Pharmacology, Wiley, Vol. 172, No. 14 ( 2015-07), p. 3671-3686
Abstract:
Hydrogen sulphide reduces uterine contractility and is of potential interest as a treatment for uterine disorders. The aim of this study was to explore the mechanism of sodium sulphide ( Na 2 S )‐induced relaxation of rat uterus, investigate the importance of redox effects and ion channel‐mediated mechanisms, and any interactions between these two mechanisms. Experimental Approach Organ bath studies were employed to assess the pharmacological effects of Na 2 S in uterine strips by exposing them to Na 2 S with or without Cl − channel blockers ( DIDS , NFA , IAA ‐94, T 16 A inh‐ A 01, TA ), raised KCl (15 and 75 mM), K + channel inhibitors (glibenclamide, TEA , 4‐ AP ), L ‐type Ca 2+ channel activator ( S ‐ B ay K 8644), propranolol and methylene blue. The activities of antioxidant enzymes were measured in homogenates of treated uteri. The expression of bestrophin channel 1 ( BEST ‐1) was determined by Western blotting and RT ‐ PCR . Key Results Na 2 S caused concentration‐dependent reversible relaxation of spontaneously active and calcium‐treated uteri, affecting both amplitude and frequency of contractions. Uteri exposed to 75 mM KCl were less sensitive to Na 2 S compared with uteri in 15 mM KCl . Na 2 S ‐induced relaxations were abolished by DIDS, but unaffected by other modulators or by the absence of extracellular HCO 3 − , suggesting the involvement of chloride ion channels. Na 2 S in combination with different modulators provoked specific changes in the anti‐oxidant profiles of uteri. The expression of BEST ‐1, both mRNA and protein, was demonstrated in rat uteri. Conclusions and Implications The relaxant effects of Na 2 S in rat uteri are mediated mainly via a DIDS ‐sensitive Cl − ‐pathway. Components of the relaxation are redox‐ and Ca 2+ ‐dependent.
Type of Medium:
Online Resource
ISSN:
0007-1188
,
1476-5381
DOI:
10.1111/bph.2015.172.issue-14
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2029728-2
SSG:
15,3
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