Pharmacological Studies of the Effect of Dai-kenchu-to on Spontaneous Contraction of Isolated Rabbit Jejunum.

Hayakawa, Terumasa; Kase, Yoshio; Saito, Kazuko; Hashimoto, Kazunori; Ishige, Atsushi; Komatsu, Yasuhiro; Sasaki, Hiroshi

doi:10.1540/jsmr.35.55

Cited by 37 publications

(32 citation statements)

References 9 publications

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“…In animal experiments, DKT increases dog intestinal motility in vivo (Furukawa et al, 1995). DKT evokes contractions in isolated intestine of rabbit and guinea pig (Kurosawa et al, 1998;Hayakawa et al, 1999b;Satoh et al, 2001aSatoh et al, , 2001b. In contrast, DKT inhibits carbachol induced contraction in rat colon (Tulimat et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Zanthoxylum fruit contracted smooth muscle preparations of rabbit jejunum and guinea pig ileum through ACh release (Kurosawa et al, 1998;Hayakawa et al, 1999b;Satoh et al, 2001a). On the other hand dried ginger root relaxed rabbit jejunum (Hayakawa et al, 1999b). Therefore multiple actions of DKT may be produced as a result of mixture of these herbs.…”

Section: Discussionmentioning

confidence: 99%

“…DKT seems to improve postoperative quality of life (QOL) of patients after surgery for gastrointestinal disorders, since it makes possible for patients to shorten their duration of hospitalization (Endo et al, 2006). DKT ameliorates gastrointestinal dysfunction through various effects, such as contraction and relaxation of smooth muscles (Furukawa et al, 1995;Kurosawa et al, 1998;Hayakawa et al, 1999b;Satoh K et al, 2001aSatoh K et al, , 2001bTulimat et al, 2001), increase of blood flow in mesenteric artery (Murata et al, 2002) and anti-inflammatory effects (Hayakawa et al, 1999a). Thus, DKT has functional improvement in intestine.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Dai-kenchu-to on spontaneous activity in the mouse small intestine

Kito

Suzuki

2006

J. Smooth Muscle Res.

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The effects of Dai-kenchu-to (DKT), a Chinese medicine, on spontaneous activity of mouse small intestine were investigated. Experiments were carried out with tension recording and intracellular recording. DKT contracted mouse longitudinal smooth muscles in a dose dependent manner (0.1-10 mg/ml). Low concentration of DKT (0.1 mg/ml) did not contract the longitudinal muscles of mouse small intestine. DKT (0.1 mg/ml) inhibited contraction elicited by transmural nerve stimulation (TNS). DKT (1 mg/ml) evoked relaxation before contraction. The initial relaxation was abolished by N ω -nitro-L-arginine (L-NNA). DKT (10 mg/ml)-induced contraction had two components: a transient rapid contraction and a following slow contraction. Atropine inhibited DKT (1 mg/ml)-induced contraction to about 50% of control. In the presence of atropine, tetrodotoxin (TTX) inhibited the contraction elicited by DKT (1 mg/ml) to about 80%. DKT depolarized the membrane and decreased the amplitude of pacemaker potentials recorded from in situ myenteric interstitial cells of Cajal (ICC-MY) with no alteration to the frequency, duration and maximum rates of rise in the presence of nifedipine and TTX.The same results were obtained in slow waves recorded from circular smooth muscle cells. These results indicate that DKT evoked both contraction and relaxation by releasing acetylcholine, nitric oxide and other excitatory neurotransmitters in mouse small intestine. DKT had no effects on pacemaker mechanisms and electrical coupling between ICC-MY and smooth muscle cells in mouse small intestine. The results also suggest that DKT may contract smooth muscles by depolarizing the membrane directly.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Dai-kenchu-to on spontaneous activity in the mouse small intestine

Kito

Suzuki

2006

J. Smooth Muscle Res.

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“…3 In experiments with isolated intestines, DKT induced contractions in rabbit jejunum and guinea pig ileum and colon. 4,5 DKT administered directly into the stomach caused phasic contractions through cholinergic and 5-hydroxytryptamine 3 (5-HT 3 ) receptors in the gastric antrum, duodenum, and jejunum in dogs. 1 In isolated guinea pig ileum, hydroxy β-sanshool, one of the ingredients of DKT, induced contractions through the release of acetylcholine from intrinsic cholinergic nerves and tachykinins from sensory neurons.…”

Section: Introductionmentioning

confidence: 99%

Dai-Kenchu-To, a Herbal Medicine, Attenuates Colorectal Distention-induced Visceromotor Responses in Rats

Nakaya

Nagura

Hasegawa

et al. 2016

J Neurogastroenterol Motil

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Background/AimsDai-kenchu-to (DKT), a traditional Japanese herbal medicine, is known to increase gastrointestinal motility and improve ileal function. We tested our hypotheses that (1) pretreatment with DKT would block the colorectal distention-induced visceromotor response in rats, and (2) pretreatment with DKT would attenuate colorectal distention-induced adrenocorticotropic hormone (ACTH) release and anxiety-related behavior. MethodsRats were pretreated with vehicle or DKT (300 mg/kg/5 mL, per os). Visceromotor responses were analyzed using electromyography in response to colorectal distention (10,20, 40, 60, and 80 mmHg for 20 seconds at 3-minutes intervals). Anxiety-related behavior was measured during exposure to an elevated-plus maze after colorectal distention. Plasma ACTH and serum corticosterone levels were measured after exposure to the elevated-plus maze. ResultsColorectal distention produced robust contractions of the abdominal musculature, graded according to stimulus intensity, in vehicletreated rats. At 40, 60, and 80 mmHg of colorectal distention, the visceromotor responses of DKT-treated rats was significantly lower than that of vehicle-treated rats. At 80 mmHg, the amplitude was suppressed to approximately one-third in DKT-treated rats, compared with that in vehicle-treated rats. Smooth muscle compliance and the velocity of accommodation to 60 mmHg of stretching did not significantly differ between the vehicle-treated and DKT-treated rats. Similarly, the DKT did not influence colorectal distentioninduced ACTH release, corticosterone levels, or anxiety-related behavior in rats. ConclusionsOur results suggest that DKT attenuates the colorectal distention-induced visceromotor responses, without increasing smooth muscle compliance, ACTH release or anxiety-related behavior in rats.

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“…[2][3][4] We confirmed that the administration of Dai-kenchu-to causes significant increases in the levels of motilin, vasoactive intestinal polypeptide (VIP), serotonin, calcitonin gene-related peptide (CGRP), and substance P in human plasma. [5][6][7] These results indicate that the gastrointestinal motor activity of Dai-kenchu-to is closely related to changes in these neuropeptides in human plasma.…”

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confidence: 60%

Effects of Pirenzepine on Dai-kenchu-to-Induced Elevation of the Plasma Neuropeptide Levels in Humans

Sato

Inoue

Katagiri

et al. 2006

Biological & Pharmaceutical Bulletin

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Dai-kenchu-to (Da-Jian-Zhong-Tang), a traditional Japanese Kampo medicine, is prepared from three different Chinese crude drugs: ninjin (Ginseng radix), sanshou (Zanthoxyli fructus), and kankyou (Zingiberis siccaatum rhizome). Dai-kenchu-to has been used for the treatment of abdominal obstructions, including bowel obstructions and a feeling of coldness in the abdomen. Dai-kenchu-to has recently been evaluated for its clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction and its clinical efficacy has been reported.1) It has been reported that the action of Dai-kenchuto is related to both increments in gastrointestinal motility and intestinal blood flow. [2][3][4] We confirmed that the administration of Dai-kenchu-to causes significant increases in the levels of motilin, vasoactive intestinal polypeptide (VIP), serotonin, calcitonin gene-related peptide (CGRP), and substance P in human plasma. [5][6][7] These results indicate that the gastrointestinal motor activity of Dai-kenchu-to is closely related to changes in these neuropeptides in human plasma.Nervous mechanisms are important for the regulation of gastrointestinal motility and blood flow. A number of neuropeptides such as CGRP, substance P, and VIP have been localized immunohistochemically in sensory nerves innervating the gastrointestinal tract.8) The release of these peptides is controlled by acetylcholine (ACh) from the preganglionic fibers of the parasympathetic nerve.9-11) Muscarinic receptors are also present on the membrane of motilin-secreting cells, and ACh is a major regulator of motilin release in the gastrointestine. [12][13][14][15] Pirenzepine, an antagonist specific for muscarinic M 1 receptors, suppresses acid output and is used to treat gastritis and peptic ulcers clinically.16) It has also been shown that this drug suppresses the elevation of serum gastrin levels by acting directly or indirectly on gastrin cells (G cells). 17,18) In this study, we examined the effects of pirenzepine on Daikenchu-to-induced elevation of plasma gastrin-, motilin-, somatostatin-, VIP-, CGRP-, and substance P-immunoreactive substance (IS) levels and the area under the plasma neuropeptides concentration-time curve from 0 to 240 min (AUC 0→240 min ) in human volunteers. VOLUNTEERS, MATERIALS, AND METHODSMaterials Dai-kenchu-to (TJ-100), prepared as a dried extract powder of Ginseng radix (3.0 g), Zanthoxyli fructus (2.0 g), and Zingiberis siccaatum rhizome (5.0 g) were purchased from Tsumura Co. Ltd. (Tokyo, Japan). Pirenzepine (Gastrozepine tablets) was purchased from Boehringer Ingelheim Co. Ltd. (Hyogo, Japan). The placebo was excipient alone (glucose and maltose) for the above formulations.Synthetic human gastrin I (2-17) was purchased from Sigma Chemicals (St. Louis, MO, U.S.A.) and the VIP fragment peptide was supplied by Professor H. Yajima (Kyoto University, Kyoto, Japan). Antisera to gastrin (A600/R1B), VIP (A6054/R1B), and CGRP were purchased from Biogenesis (Poole, U.K.). Antisera to somatos...

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Pharmacological Studies of the Effect of Dai-kenchu-to on Spontaneous Contraction of Isolated Rabbit Jejunum.

Cited by 37 publications

References 9 publications

Effects of Dai-kenchu-to on spontaneous activity in the mouse small intestine

Effects of Dai-kenchu-to on spontaneous activity in the mouse small intestine

Dai-Kenchu-To, a Herbal Medicine, Attenuates Colorectal Distention-induced Visceromotor Responses in Rats

Effects of Pirenzepine on Dai-kenchu-to-Induced Elevation of the Plasma Neuropeptide Levels in Humans

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