Carbachol (CCh, 10^-6M) induced biphasic contraction of longitudinal muscle of the guinea pig stomach, consisting of rapid phasic contraction and contracture. The contracture was almost completely inhibited by sodium nitroprusside (SNP, 10^-6M) and S-nitroso-N-acetyl penicillamine (SNAP, 10^-6M). A membrane permeable analogue of cyclic GMP, 8Br-cGMP (10^-4M), also inhibited the CCh-induced contracture. Although a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase, 1-H- [1, 2, 4] oxadiazolo- [4, 3-a] quinoxalin-1-one (ODQ; 10^-6M), reduced the inhibitory action of SNP, it did not affect the inhibitory action of 8Br-cGMP, indicating that the effect of SNP was developed via cyclic GMP production in the presence of D600. Charybdotoxin (10^-7M), an inhibitor of Ca²⁺-activated K⁺ channel, did not influence on the CCh-induced contracture. On the other hand, CCh induced a depolarization of the longitudinal muscle cell membrane (from -6 mV to -45 mV) in the presence of 10^-6 M D600, but SNP did not affect the depolarization. These results suggest that in the presence of D600 SNP induces relaxation of CCh-induced contracture of the longitudinal muscle of the guinea pig stomach via cyclic GMP but not membrane potential dependent mechanism

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High concentration of acetylcholine (ACh) caused a rapid and long-lasting relaxation response in age-matched controls, whereas this response was significantly weaker in streptozotocin (STZ)-diabetic and cholesterol-fed mice. The levels of basal and ACh-stimulated cyclic GMP in the aorta was also significantly smaller in STZ-diabetic and cholesterol-fed mice. The attenuated relaxation responses to ACh in both STZ-diabetic and cholesterolfed mice were ameliorated by the chronic administration of cholestyramine. A prior incubation of aortic strips with superoxide dismutase (SOD, 60U/ml) improved the recovery phase of the relaxation of diabetic aorta after single administration of ACh, whereas SOD had no effects on ACh-induced relaxation of aortic strips from cholesterol-fed mice. These results suggest that superoxide anion may be responsible for an impairment of endothelium-dependent relaxation of aorta from STZ-induced diabetic mice. It is further suggested that impairment of endothelium-dependent relaxation in STZ-diabetic and cholesterol-fed mice may be caused by different mechanisms.

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To confirm the usefulness of Dai-kenchu-to for intestinal obstruction, investigation of the effects of Dai-kenchu-to on postoperative intestinal adhesion was conducted. Repeated administrations of Dai-kenchu-to (100 or 300 mg/kg) significantly inhibited the formation of intestinal obstruction. Motor disturbance and inflammation are thought to be involved in the etiology of intestinal adhesion. A single treatment of Dai-kenchu-to (300mg/kg) significantly reduce intestinal transit time in postoperative ileus and chemically-induced ileus. Dai-kenchu-to (10^-4 g/ml) significantly inhibited COX-2 activity.
These results suggest that Dai-kenchu-to prevents postoperative intestinal adhesion by gastroprokinetic and anti-inflammatic effects. Dai-kenchu-to thus demonstrates positive effect on postoperative ileus.

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We studied the effects of Dai-kenchu-to on the spontaneous contraction in isolated rabbit jejunum. Dai-kenchu-to (10^-3g/ml) increased jejunal contraction, such as phasic-like contraction and contractile amplitude. Zanthoxyli Fructus (2×10^-4g/ml) exhibited an action identical to that of Dai-kenchu-to. While Zingiberis Siccatum Rhizoma (5×10^-4g/ml) continuously decreased the amplitude of contraction. Ginseng Radix (3×10^-4g/ml) and Saccharum Granorum (8×10^-3g/ml) had no effect on spontaneous contraction. Dai-kenchu-to and Zanthoxyli Fructus reversed the decrease of contraction produced by atropine. However, phasic-like contraction induced in the absence of atropine was antagonized by atropine. Dai-kenchu-to and Zingiberis Siccatum Rhizoma further decreased spontaneous contraction in the presence of tetrodotoxin.
It was clarified that Dai-kenchu-to possesses gastroprokinetic effect, and Zanthoxyli Fructus mainly contributed to this effect. It was suggested that the cholinergic and non-cholinergic nervous systems were involved in increasing intestinal motility. It was also suggested that Dai-kenchu-to acted on multiple points of the intestine, and actions at these points might intensify to improve ileus.

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