Comparative effects of K+ channel modulating agents on contractions of rat intestinal smooth muscle

Davies, M.; McCurrie, Janice R.; Wood, Diana

doi:10.1016/0014-2999(95)00740-7

Cited by 21 publications

(28 citation statements)

References 29 publications

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“…Incubation period was based on preliminary experiments showing such time was sufficient for LDD175 to exert relaxant activity. In the next separate experiments, the K + channel opening activity of LDD175 was explored as previously described (Davies et al, 1996;Kobayashi et al, 2000;Malysz et al, 2004). After equilibration, the preparations were contracted with high K + (20 or 60 mM KCl) and the responses were allowed to reach a plateau (after 10 min).…”

Section: In Vitro Experimentsmentioning

confidence: 99%

Inhibition of intestinal motility by the putative BKCa channel opener LDD175

et al. 2009

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LDD175 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid) is a benzofuroindole compound characterized previously as a potent opener of the large conductance calcium activated (BK(Ca)) channels. Activators of the BK(Ca) channels are potential therapies for smooth muscle hyperactivity disorders. The present study investigates the influence of LDD175 on the mechanical activity of the ileum smooth muscle. LDD175 inhibited spontaneous contractions of the ileum in a concentration-dependent manner (pEC(50)=5.9 +/- 0.1) (E (max)=96 +/- 1.0% at 100 muM, n=3). It also remarkably inhibited contractions due to acetylcholine (ACh) (pEC(50)=5.3 +/- 0.1)(E (max)=97.7 +/- 2.3%, n=6) and electrical field stimulation (EFS) (pEC(50)=5.5 +/- 0.1) (E (max)=83.3 +/- 6.0%, n=6). In strips precontracted by 20 mM KCl, LDD175 significantly reduced the contractions yielding a pEC(50) of 6.1 +/- 0.1 and E (max) of 96.6 +/- 0.9%, (n=6). In 60 mM KCl, a concentration-dependent inhibition was observed with respective pEC(50) and E (max) values of 4.1 +/- 0.1 and 50.8 +/- 5.0% (n=3). BK(Ca) channel blockers iberiotoxin (IbTX) and tetraethylammonium chloride (TEA, 1 mM) attenuated the relaxative effect of LDD175 but not barium chloride (BaCl(2)), and glibenclamide (K(IR) and K(ATP) channel blockers, respectively). These data demonstrate the antispasmodic activity of LDD175 attributable to the potentiation of the BK(Ca) channels.

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Section: In Vitro Experimentsmentioning

confidence: 99%

Inhibition of intestinal motility by the putative BKCa channel opener LDD175

et al. 2009

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“…Therefore, the effect of β-adrenergic-mediated vasorelaxation was not involved in the pathway. K + channels play an important role in regulating resting arterial membrane potential and vascular tone [31][32][33] . The direct activation of K + channels on arterial smooth muscle cells generally hyperpolarizes the cell membrane, results in the inhibition of Ca 2+ influx through VDCC, and interrupts smooth muscle contraction.…”

Section: Discussionmentioning

confidence: 99%

Endothelium-independent vasorelaxant effect of 20(S)-protopanaxadiol on isolated rat thoracic aorta

et al. 2016

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Aim: Ginsenosides are considered to be the major pharmacologically active ginseng constituents, whereas 20(S)-protopanaxadiol [20(S)-PPD] is the active metabolite of ginsenosides in gut. In this study we investigated the effect of 20(S)-PPD on isolated rat thoracic aortas as well as its vasorelaxant mechanisms. Methods: Aortic rings with or without endothelium were prepared from Wistar rats and suspended in organ-chambers. The changes in tension of the preparations were recorded through isometric transducers connected to a data acquisition system. The aortic rings were precontracted with phenylephrine (PE, 1 µmol/L) or high-K + (80 mmol/L).

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“…The substance that selectively relaxes the contractions induced by low K + is considered to be potassium channel opener, while Ca ++ entry blockers inhibit both low and high K + -induced contractions equally, and these experiments allow distinguishing K + channel activation from CCB mechanism (Hamilton et al, 1986;Kishii et al, 1992;Gopalakrishnan et al, 2004). The K + channel opening effect was confirmed, when the inhibition of low K + -induced contractions was prevented in the presence of glibenclamide, a blocker of ATP-dependent K + channels (Frank et al, 1994 ;Davies et al, 1996). Cromakalim, a prototypical KATP channel opener (Brown and Raeburn, 1991;Deitmer et al, 1992;Moura et al, 1993) produced similar results to that of the M. alba extract, except that it produced no effect on high K + -induced contractions, while verapamil, a Ca ++ antagonist (Fleckenstein, 1977) inhibited low and high K + -induced contractions at similar concentrations.…”

Section: Discussionmentioning

confidence: 99%