The effects of SQ-22536 (an adenylate cyclase inhibitor), ODQ (a guanylate cyclase inhibitor), RP-8-CPT-cGMPS (a PKG inhibitor) and L-NAME (a nonselective nitric oxide synthase inhibitor) on pacemaker activity inhibition by GRe in cultured ICC clusters. (A) The pacemaker activity of ICCs exposed to GRe in the presence of SQ-22536 (100μM). SQ-22536 had no effect on the inhibition of pacemaker activity by GRe. The pacemaker activity of ICCs exposed to quercetin in the presence of (B) ODQ (100μM), (C) RP-8-CPT-cGMPS (10μM), or (D) L-NAME (100μM). The inhibitors ODQ, RP-8-CPT-cGMPS, and L-NAME blocked pacemaker activity inhibition by GRe. (E) The graph summarizes the response to GRe in the presence of SQ-22536, ODQ, RP-8-CPT-cGMPS, and L-NAME. The bars represent the mean ± the standard deviation. ** p < 0.01. CTRL, control; GRe, ginsenoside Re; ICC, interstitial cell of Cajal; L-NAME, L-NG-nitroarginine methyl ester; ODQ, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; PKG, protein kinase C; RP, RP-8-CPT-cGMPS.