Hydroxy-α sanshool induces colonic motor activity in rat proximal colon: a possible involvement of KCNK9.
Bottom Line: Hydroxy-α sanshool (HAS), a readily absorbable active ingredient of TU-100 and a KCNK3/KCNK9/KCNK18 blocker as well as TRPV1/TRPA1 agonist, has been investigated for its effects on colonic motility.The effect of HAS was unaltered by TRPV1/TRPA1 antagonists and desensitization.HAS may evoke strong LDC possibly via blockage of the neural KCNK9 channel in the colonic myenteric plexus.
Affiliation: Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan;Show MeSH
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Mentions: It is not known whether HAS and HBS inhibit rat KCNK3 and/or KCNK9. Thus we conducted two electrode voltage-clamp assays using Xenopus oocytes expressing rat KCNK3 or KCNK9. Because both channels were reported to be regulated by extracellular pH, application of pH 6.5 solution was used as a positive control. Inhibitory effect of test compounds were determined with a holding potential of +60 mV. Lid was used as a nonselective KCNK channel blocker, which strongly inhibited both KCNK3 and KCNK9. As shown in Fig. 6A, HAS showed significant and dose-dependent inhibition against KCNK3 and KCNK9 whereas HBS inhibited only KCNK3. These results were comparable to those observed for murine KCNKs (1).
Affiliation: Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan;