title: Chloride channels mediate sodium sulphide-induced relaxation in rat uteri.
abstract: OBJECTIVE
  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 (Na2 S)-induced relaxation of rat uterus, investigate the importance of redox effects and ion channel-mediated mechanisms, and any interactions between these two mechanisms.
  
  
  METHODS
  Organ bath studies were employed to assess the pharmacological effects of Na2 S in uterine strips by exposing them to Na2 S with or without Cl(-) channel blockers (DIDS, NFA, IAA-94, T16Ainh-A01, TA), raised KCl (15 and 75 mM), K(+) channel inhibitors (glibenclamide, TEA, 4-AP), L-type Ca(2+) channel activator (S-Bay 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.
  
  
  RESULTS
  Na2 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 Na2 S compared with uteri in 15 mM KCl. Na2 S-induced relaxations were abolished by DIDS, but unaffected by other modulators or by the absence of extracellular HCO3 (-) , suggesting the involvement of chloride ion channels. Na2 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
  The relaxant effects of Na2 S in rat uteri are mediated mainly via a DIDS-sensitive Cl(-) -pathway. Components of the relaxation are redox- and Ca(2+) -dependent.
authors: Department of Physiology, Institute for Biological Research 'Siniša Stanković', University of Belgrade, Belgrade, Serbia.
authors: Ana
authors: A
authors: Mijušković
authors: Department of Physiology, Institute for Biological Research 'Siniša Stanković', University of Belgrade, Belgrade, Serbia.
authors: Aleksandra Nikolić
authors: AN
authors: Kokić
authors: Department of Physiology, Institute for Biological Research 'Siniša Stanković', University of Belgrade, Belgrade, Serbia.
authors: Zorana Oreščanin
authors: ZO
authors: Dušić
authors: Department of Physiology, Institute for Biological Research 'Siniša Stanković', University of Belgrade, Belgrade, Serbia.
authors: Marija
authors: M
authors: Slavić
authors: Department of Physiology, Institute for Biological Research 'Siniša Stanković', University of Belgrade, Belgrade, Serbia.
authors: Mihajlo B
authors: MB
authors: Spasić
authors: Department of Physiology, Institute for Biological Research 'Siniša Stanković', University of Belgrade, Belgrade, Serbia.
authors: Duško
authors: D
authors: Blagojević
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000378:metabolism*; D005260:Female; D009126:Muscle Relaxation / Q000187:drug effects*; D009215:Myometrium / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D013440:Sulfides; C033479:sodium sulfide