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Inhibition of intestinal motility by the putative BKCa channel opener LDD175
| Content Provider | Semantic Scholar |
|---|---|
| Author | Peña, Ike Campomayor Dela Yoon, Seo Young Kim, Sung Mok Lee, Geum Seon Park, Chul-Seung Kim, Yong Chul Cheong, Jae Hoon |
| Copyright Year | 2009 |
| Abstract | 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 (BKCa) channels. Activators of the BKCa 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 (pEC50=5.9 ± 0.1) (Emax=96 ± 1.0% at 100 μM, n=3). It also remarkably inhibited contractions due to acetylcholine (ACh) (pEC50=5.3 ± 0.1)(Emax=97.7 ± 2.3%, n=6) and electrical field stimulation (EFS) (pEC50=5.5 ± 0.1) (Emax=83.3 ± 6.0%, n=6). In strips precontracted by 20 mM KCl, LDD175 significantly reduced the contractions yielding a pEC50 of 6.1 ± 0.1 and Emax of 96.6 ± 0.9%, (n=6). In 60 mM KCl, a concentration-dependent inhibition was observed with respective pEC50 and Emax values of 4.1 ± 0.1 and 50.8 ± 5.0% (n=3). BKCa channel blockers iberiotoxin (IbTX) and tetraethylammonium chloride (TEA, 1 mM) attenuated the relaxative effect of LDD175 but not barium chloride (BaCl2), and glibenclamide (KIR and KATP channel blockers, respectively). These data demonstrate the antispasmodic activity of LDD175 attributable to the potentiation of the BKCa channels. |
| Starting Page | 413 |
| Ending Page | 420 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| DOI | 10.1007/s12272-009-1315-x |
| PubMed reference number | 19387586 |
| Journal | Medline |
| Volume Number | 32 |
| Alternate Webpage(s) | https://page-one.live.cf.public.springer.com/pdf/preview/10.1007/s12272-009-1315-x |
| Alternate Webpage(s) | https://page-one.springer.com/pdf/preview/10.1007/s12272-009-1315-x |
| Alternate Webpage(s) | https://doi.org/10.1007/s12272-009-1315-x |
| Journal | Archives of pharmacal research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
