title: 4-Chloro-7-trifluoromethyl-10H- benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (TBIC), a putative BK(Ca) channel opener with uterine relaxant activities.
abstract: In the present study, we examined the uterine relaxant activity of 4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid (TBIC), a putative opener of the large conductance Ca(2+)-activated K(+) (BK(Ca)) channel. TBIC concentration-dependently inhibited spontaneous uterine contractions (EC(50) = 4.63 μmol/l; E(max) = 94.85 ± 1.85%; 100 μmol/l, n = 6). It also reduced contractions induced by oxytocin (EC(50) = 4.10 μmol/l; E(max) = 84.3 ± 3.83%; 100 μmol/l, n = 6), prostaglandin F(2)(α) (EC(50) = 2.14 μmol/l; E(max) = 73.70 ± 5.21%; 100 μmol/l, n = 6) and acetylcholine (EC(50) = 4.37 μmol/l; E(max) = 83.67 ± 4.82; 100 μmol/l, n = 6). TBIC decreased KCl (20 mmol/l) -induced contractions (EC(50) = 3.04 μmol/l; E(max) = 94.0 ± 3.12%; 100 μmol/l, n = 6) indicating its K(+) channel opening activity. BK(Ca) channel blockers penitrem A (100 nmol/l) and tetraethylammonium chloride (1 mmol/l) attenuated the inhibitory activities of TBIC (p < 0.001) but not other K(+) channel blockers such as barium chloride and glibenclamide (K(IR) and K(ATP) channel blockers, respectively). These results demonstrate the uterine relaxant effects of TBIC in a mechanism of action largely referable to the potentiation of the BK(Ca) channels. We have provided evidence for the potential use of TBIC as a tocolytic agent and support for the utility of BK(Ca) channel openers in pathophysiologic conditions involving smooth muscle hyperactivity.
authors.affiliation: College of Pharmacy, Sahmyook University, Seoul, Korea.
authors.forename: Hyung Seok
authors.initials: HS
authors.lastname: Ahn
authors.forename: Ike
authors.initials: I
authors.lastname: dela Peña
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D002264:Carboxylic Acids / Q000493:pharmacokinetics / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects; D010121:Oxytocin / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015149:Tocolytic Agents / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects / Q000502:physiology
chemical_list: C509565:7-trifluoromethyl-10H-benzo(4,5)furo(3,2-b)indole-1-carboxylic acid; D017609:Barium Compounds; D002264:Carboxylic Acids; D002712:Chlorides; D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D011461:Prostaglandins F, Synthetic; D015149:Tocolytic Agents; C024986:barium chloride; D010121:Oxytocin; D011189:Potassium Chloride; D000109:Acetylcholine; D005905:Glyburide