title: Retigabine diminishes the effects of acetylcholine, adrenaline and adrenergic agonists on the spontaneous activity of guinea pig smooth muscle strips in vitro.
abstract: OBJECTIVE
  The aim of this study is to evaluate the effect of retigabine on the smooth muscle response to acetylcholine, adrenaline, α-and β-adrenoceptor agonists.
  
  
  METHODS
  We studied the change in the spontaneous smooth muscle contraction of guinea pig gastric corpus strips before and after 20-min treatment with 2μM retigabine. We also evaluated the effect of retigabine on the smooth muscle response to 10μM acetylcholine, 1 and 10μM adrenaline, 1μM methoxamine, 0.1μM p-iodoclonidine and 10μM isoproterenol.
  
  
  RESULTS
  We observed a significant reduction in the effects of all studied mediators and agonists when they were added to organ baths in the presence of retigabine. Retigabine diminished the effect of acetylcholine on the spontaneous smooth muscle activity. The effect was fully antagonized by XE-991 (Kv7 channel blocker), which supports our hypothesis about the role of KCNQ channels in the registered changes. The increase in the contraction force after adding of 1μM adrenaline, methoxamine, and 0.1μM p-iodoclonidine was also significantly smaller in presence of retigabine. However, comparing the effect of 10μM adrenaline on the contractility before and after treatment with retigabine, we observed increased contractility when retigabine was present in the organ baths.
  
  
  CONCLUSIONS
  A possible explanation for the observed diminished effects of mediators and receptor agonists is that the effect of retigabine on smooth muscle contractility is complex. The membrane hyperpolarization, the interaction between Kv7 channels and adrenoceptors, and the influence on signaling pathways may contribute to the summary smooth muscle response.
authors.affiliation: Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria. Electronic address: apostolova1212@gmail.com.
authors.forename: Elisaveta
authors.initials: E
authors.lastname: Apostolova
authors.affiliation: Department of Biophysics, Faculty of Pharmacy, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria.
authors.forename: Plamen
authors.initials: P
authors.lastname: Zagorchev
authors.affiliation: Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria.
authors.forename: Vesela
authors.initials: V
authors.lastname: Kokova
authors.affiliation: Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University-Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria.
authors.forename: Lyudmil
authors.initials: L
authors.lastname: Peychev
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D051656:KCNQ Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008729:Methoxamine / Q000378:metabolism / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010655:Phenylenediamines / Q000494:pharmacology*; D011897:Random Allocation; D013270:Stomach / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000322:Adrenergic Agonists; D000873:Anthracenes; D002219:Carbamates; D018679:Cholinergic Agonists; D051656:KCNQ Potassium Channels; D010655:Phenylenediamines; C053113:4-iodoclonidine; C101866:ezogabine; D008729:Methoxamine; D007545:Isoproterenol; D003000:Clonidine; D000109:Acetylcholine; D004837:Epinephrine
keywords: Acetylcholine; Adrenaline; KCNQ; α-adrenoceptor; β-adrenoceptor