4-Chloro-7-Trifluoromethyl-10H-Benzo[4,5]furo[3,2-b]Indole-1-Carboxylic Acid (TBIC), a Putative BKCa Channel Opener with Uterine Relaxant Activities

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 Ca2+-activated K+ (BKCa) channel. TBIC concentration-dependently inhibited spontaneous uterine contractions (EC50 = 4.63 mu mol/l; E-max = 94.85 +/- 1.85%; 100 mu mol/l, n = 6). It also reduced contractions induced by oxytocin (EC50 = 4.10 mu mol/l; E-max = 84.3 +/- 3.83%; 100 mu mol/l, n = 6), prostaglandin F-2 alpha (EC50 = 2.14 mu mol/l; E-max = 73.70 +/- 5.21%; 100 mu mol/l, n = 6) and acetylcholine (EC50 = 4.37 mu mol/l; E-max = 83.67 +/- 4.82; 100 mu mol/l, n = 6). TBIC decreased KCl (20 mmol/l) -induced contractions (EC50 = 3.04 mu mol/l; E-max = 94.0 +/- 3.12%; 100 mu mol/l, n = 6) indicating its K+ channel opening activity. BKCa 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 BKCa channels. We have provided evidence for the potential use of TBIC as a tocolytic agent and support for the utility of BKCa channel openers in pathophysiologic conditions involving smooth muscle hyperactivity. Copyright (C) 2011 S. Karger AG, Basel