Potassium channels opener pinacidil have multiple effects on KCl-elicited contractions of isolated non-pregnant rat uterus

Abstract

The effects of K+ channel opener, pinacidil on contractions provoked by contraction-stimulating KCl were investigated on isolated uterus of non-pregnant rats in oestrus. Pinacidil produced a more potent inhibition of 20 mM KCl-elicited contractions (pD2 = 6.57 μM) than of 40 or 80mMKCl-elicited contractions (pD2=5.11 and 5.19 μM, respectively). Glibenclamide, a selective blocker of adenosine triphosphate (ATP)-sensitive K+ (KATP) channels, antagonized the pinacidil-induced inhibition of contractions elicited by 20 mM KCl in a competitive manner. However, the pinacidil-induced inhibition of contractions provoked by 40 and 80 mM KCl glibenclamide was unable to prevent them. Pinacidil ability to completely relax the non-pregnant uterus pre-contracted with K+-rich solution suggests that K+ channelindependent mechanism(s) also plays a part in its relaxant effect.

U ovom radu su prikazani efekti pinacidila, koji ima osobinu da otvara kalijumove kanale, na kontrakcije izazvane kalijum hloridom na modelu izolovanog negravidnog uterusa ženki pacova tokom estrusa. Pinacidil dovodi do snažnije inhibicije kontrakcija izazvanih sa 20mM KCl (pD2= 6.57 μM) u poređenju sa kontrakcijama izazvanim sa 40 ili 80 mM KCl (pD2 = 5.11 i 5.19 μM). Poznato je da je glibenclamid selektivni blokator adenozin-3-fosfat senzitivnih K+ (KATP) kanala antagonizuje pinacidilom indukovanu kompetitivnu inhibiciju kontrakcija izazvanih pomoću 20 mM KCl-a. Međutim, pinacidilom indukovana inhibicija kontrakcija, izazvanih sa 40 i 80 mM KCl-a nije se mogla prevenirati glibenclamidom. Sposobnost pinacidila da dovede do potpune relaksacije negravidnog uterusa ženki pacova pre kontrakcije izazvane rastvorom kalijuma ukazuje na to da u relaksaciji učestvuje i mehanizam nezavisan od kalijumovih kanala.