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...