Chloride channels mediate sodium sulphide-induced relaxation in rat uteri
2015
Аутори:
Mijušković, AnaNikolić-Kokić, Aleksandra
Oreščanin-Dušić, Zorana
Slavić, Marija
Spasić, Mihajlo
Blagojević, Duško
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2015 The British Pharmacological Society
Метаподаци
Приказ свих података о документуАпстракт:
Background and PurposeHydrogen 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
(Na2S)-induced relaxation of rat uterus, investigate the importance of
redox effects and ion channel-mediated mechanisms, and any interactions
between these two mechanisms.
Experimental ApproachOrgan bath studies were employed to assess the
pharmacological effects of Na2S in uterine strips by exposing them to
Na2S with or without Cl- channel blockers (DIDS, NFA, IAA-94,
T16Ainh-A01, TA), raised KCl (15 and 75mM), K+ channel inhibitors
(glibenclamide, TEA, 4-AP), L-type Ca2+ 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.
Key ResultsNa(2)S caused concentration-dependent reversible relaxation
of spontaneously active and calcium-treated uteri, affecting both
amplitude and frequency of contractions. Uteri exposed to 75mM KCl were
less sensitive to Na2S compared with uteri in 15mM KCl. Na2S-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. Na2S 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 ImplicationsThe relaxant effects of Na2S in rat uteri
are mediated mainly via a DIDS-sensitive Cl--pathway. Components of the
relaxation are redox- and Ca2+-dependent.
Извор:
British Journal of Pharmacology, 2015, 172, 14, SI, 3671-3686
DOI: 10.1111/bph.13161
ISSN: 0007-1188
PubMed: 25857480