title: [Ontogeny of sulphonylurea-binding regulatory subunits of K(ATP) channels in the pregnant rat myometrium].
abstract: K(ATP) channels are composed of sulphonylurea receptors (SURs) and potassium inward rectifiers (Kir(6.x)) that assemble to form a large octameric channel. This study was designed to examine the expression and role of sulphonylurea-binding regulatory subunits 1 [SUR1 (ABCC8)] and 2 [SUR2 (ABCC9)] of the K(ATP) channels in the pregnant rat myometrium with particular regard to the contractility. RT-PCR and Western blot analysis were performed to detect the presence of SUR1 and SUR2. The SUR1 levels were markedly increased in the early stages of pregnancy. The highest level was detected on day 6 of pregnancy, while in the late stages the levels of SUR1 were significantly decreased. The SUR2 level remained unchanged throughout pregnancy. The SUR-non-selective diazoxide and the SUR2-selective pinacidil inhibited oxytocin-induced contractions. Glibenclamide, a K(ATP) channel blocker, antagonized both pinacidil and diazoxide-induced relaxations. It was established that SURs are responsible for pharmacological reactivity of K(ATP) channel openers. We conclude that, both SURs are involved in the K(ATP) channel in the pregnant rat myometrium. It may further be concluded that "pinacidil-like" K(ATP) channel openers may be of therapeutic relevance as tocolytic agents in the future.
authors.affiliation: Szegedi Tudományegyetem Gyógyszerésztudományi Kar, Gyógyszerhatástani és Biofarmáciai Intézet, Szeged, Eötvös utca 6. - 6720.
authors.forename: Norbert
authors.initials: N
authors.lastname: Lovász
authors.forename: Eszter
authors.initials: E
authors.lastname: Ducza
authors.forename: Róbert
authors.initials: R
authors.lastname: Gáspár
authors.forename: György
authors.initials: G
authors.lastname: Falkay
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D003981:Diazoxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D010121:Oxytocin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020110:Pinacidil / Q000037:antagonists & inhibitors / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D020033:Protein Isoforms / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000378:metabolism*; D064233:Sulfonylurea Receptors; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D018528:ATP-Binding Cassette Transporters; C577509:Abcc8 protein, rat; C577512:Abcc9 protein, rat; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D021122:Protein Subunits; D012333:RNA, Messenger; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D015149:Tocolytic Agents; D010121:Oxytocin; D020110:Pinacidil; D003981:Diazoxide; D005905:Glyburide