Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Satoh, Kaneo; Hashimoto, Kazunori; Hayakawa, Terumasa; Ishige, Atsushi; Kaneko, Michiko; Ogihara, Soichiro; Kurosawa, Susumu; Yakabi, Koji; Nakamura, Takashi

doi:10.1254/jjp.86.32

Cited by 59 publications

(61 citation statements)

References 22 publications

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“…Capsaicin, a vanilloid receptor agonist, stimulates capsaicin-sensitive afferent neurons, which releases CGRP and substance P from their nerve endings. [26][27][28][29] In previous reports, Zingiberis rhizoma extract and 6-shogaol produced an increase in intestinal blood flow, and the CGRP receptor antagonist CGRP (8-37) completely abolished the reaction.…”

Section: Resultsmentioning

confidence: 99%

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

Sato

Katagiri

Inoue

et al. 2004

Biological & Pharmaceutical Bulletin

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Sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptides [calcitonin gene-related peptide (CGRP), substance P, etc.], which play various physiologic roles and are gastroprotective. To determine whether the pharmacologic effects of Dai-kenchu-to (DKCT) on the gastrointestine are due to changes in gastrointestinal mucosa regulatory peptide levels, we examined the effects of the DKCT on the levels of CGRP-like immunoreactive substances (IS) and substance P-IS in plasma taken from five healthy subjects. A single oral administration of DKCT 7.5 g caused significant increases in plasma CGRP-IS at 40 min, and in substance P-IS levels at 20 and 60 min, compared with a placebo group. The present study may indicate that the pharmacologic action of DKCT is closely related to changes in CGRP-and substance P-IS levels.

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Section: Resultsmentioning

confidence: 99%

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

Sato

Katagiri

Inoue

et al. 2004

Biological & Pharmaceutical Bulletin

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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%

“…DKT releases ACh from cholinergic nerve endings via activation of 5HT4 receptors in guinea pig ileum (Satoh et al, 2001b). Since 5HT4 receptors are also expressed in enteric nervous system in mouse small intestine (Liu et al, 2005), DKT may also activate 5HT4 receptors at the ends of cholinergic nerve to enhance the release of ACh in mouse small intestine.…”

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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“…47,48) Dai-kenchu-to stimulates substance P release and induces contractions in guinea pig ileum. 49) Schmidt et al reported that muscarinic receptors are present on the intrinsic substance P-producing neurons and inhibit the release of substance P in porcine ileum. 11) In our study, Dai-kenchu-to raised plasma substance P-IS levels after administration to healthy volunteers, while plasma substance P-IS levels after the administration of Dai-kenchu-to with pirenzepine pretreatment tended to decrease compared with Dai-kenchu-to alone.…”

Section: Discussionmentioning

confidence: 99%

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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Mechanism of Atropine-Resistant Contraction Induced by Dai-kenchu-to in Guinea Pig Ileum

Cited by 59 publications

References 22 publications

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

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

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

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