title: ATP-sensitive potassium channels modulate in vitro tocolytic effects of β₂-adrenergic receptor agonists on uterine muscle rings in rats in early but not in late pregnancy.
abstract: OBJECTIVE
  To investigate whether ATP-sensitive potassium (K(ATP)) channels modulate the tocolytic effect of β2-adrenergic receptor (β2-AR) agonists (ritodrine and salmeterol) in early-pregnant (day 6) and late-pregnant (day 22) rat uterus in vitro, in order to examine the relation between the K(ATP) channel sulphonylurea-binding regulatory subunit (SUR) expression and pharmacological reactivity of β2-AR agonists.
  
  
  METHODS
  The tocolytic effects of ritodrine and salmeterol (10(-10)-10(-5) M) on spontaneous rhythmic contractions were investigated cumulatively, alone, or in the presence of the K(ATP) channel blocker glibenclamide (10(-6) M) and the K(ATP) channel opener pinacidil (10(-9)-10(-7) M) after 5-min preincubation.
  
  
  RESULTS
  β2-AR agonist induced myometrial relaxation was inhibited by glibenclamide and enhanced by pinacidil on day 6, when SUR1 expression levels were high. Neither glibenclamide nor pinacidil mediated tocolytic effect was measured on day 22.
  
  
  CONCLUSIONS
  Low expression of the K(ATP) channels at the end of gestation may facilitate enhanced excitability and contractility in the rat myometrium. The combination of a betamimetic and a K(ATP) channel opener will therefore not be of therapeutic relevance in the treatment of preterm delivery.
authors.forename: Norbert
authors.initials: N
authors.lastname: Lovasz
authors.forename: Andrea
authors.initials: A
authors.lastname: Koncz
authors.forename: Dora
authors.initials: D
authors.lastname: Domokos
authors.forename: Robert
authors.initials: R
authors.lastname: Gaspar
authors.affiliation: György Falkay, Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, H-6701, P.O. Box 121, Hungary, falkay@pharm.u-szeged.hu.
authors.forename: György
authors.initials: G
authors.lastname: Falkay
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012312:Ritodrine / Q000494:pharmacology; D000068299:Salmeterol Xinafoate; D064233:Sulfonylurea Receptors / Q000378:metabolism; D015149:Tocolytic Agents / Q000494:pharmacology*
chemical_list: C577509:Abcc8 protein, rat; D058666:Adrenergic beta-2 Receptor Agonists; D054086:KATP Channels; D026902:Potassium Channel Blockers; D064233:Sulfonylurea Receptors; D015149:Tocolytic Agents; D000068299:Salmeterol Xinafoate; D020110:Pinacidil; D012312:Ritodrine; D000420:Albuterol; D005905:Glyburide