Capsaicin inhibition of CCh-induced colonic Cl-secretion by selective blockade of TRPV4 channels.A and B, summary data comparing carbachol (CCh, 100 μM, n = 5)- or caffeine (Caf, 10 mM, n = 5)-stimulated distal colonic Isc between WT mice and TRPV4 KO mice. C, representative time courses and summary data showing the inhibitory effect of TRPV4 blockers RN1734 (50 μM, n = 5) and HC067047 (HC, 10 μM, n = 7) on CCh (50 μM, n = 6) -stimulated distal colonic Isc in the absence or the presence of TRPV4 activator RN1747 (40 μM) in WT mice. D, representative time courses and summary data showing the inhibitory effect of capsaicin (Cap, 30 uM, n = 5) on CCh (50 μM, n = 5) -stimulated distal colonic Isc in the absence or the presence of TRPV4 activator RN1747 (40 μM) in WT mice. E, representative time courses and summary data showing the effect of Cap (30 μM, n = 5) on CCh (100 μM, n = 5)-stimulated distal colonic Isc in the absence or the presence of TRPV4 activator RN1747 (40 μM, n = 5) in TRPV4 KO mice. Ctrl represents as the control with CCh treatment only. CCh adds to serosal side, RN1747, RN1734, and HC add to both sides. The data are presented as mean ± SD. ∗p < 0.05 and ∗∗p < 0.01 were performed by Student’s t test. ns, no significant differences. Caf, caffeine; CCh, carbachol; Isc, short-circuit current; TRPV, transient receptor potential vanilloid.