Somatostatin is a gastrointestinal motility regulator and functions as an inhibitor of hormone release in digestive organs. This peptide participates in the regulation of gastrointestinal motility with motilin. [1][2][3][4][5][6] Somatostatin as a gut regulatory peptide stimulates migrating motor complex (MMC)-like activity and its analogue was the first to be used therapeutically among the gastrointestinal peptides.7) Motilin, a peptide connected with somatostatin, has a powerful fundic pouch motor-stimulating activity and is one of the most important factors controlling the regular occurrence of phase 3 contractions of the MMC. 8,9) Another gut regulatory peptide, gastrin, stimulates acid secretion, and its release is mediated by various pathways such as direct stimulation of G cells, mediation by cholinergic nerves, stimulation of gastrin-releasing peptide, stomach pH, etc. 10)Vasoactive intestinal peptide (VIP) is widely distributed in the central and peripheral nervous system. This peptide has a vasodilating effect in many vascular beds, including the peripheral systemic and splanchnic beds and the cerebral arteries, and is an important neurotransmitter for the enteric nervous system. 11,12) Hange-shashin-to (EK-14), a Kampo herbal medicine, is prepared from seven crude herbs: Pinelliae Tuber, Scutellariae Radix, Zingiberis Rhizoma, Ginseng Radix, Glycyrrhizae Radix, Zizyphi Fructus, and Coptidis Rhizoma. Hangeshashin-to is frequently used for acute or chronic gastrointestinal catarrh, fermentative diarrhea, and acute gastroenteritis. This medicine has been clinically evaluated as more effective in the treatment of chronic hypofunction of the gastrointestinal system than is Rikkunshi-to in the treatment of hyperfunctioning conditions. Recently, Hange-shashin-to has been reported to be effective against diarrhea as a side effect of carcinostatic drugs. 13)Based on empirical effects of Kampo, some gut-targeting medicines have been determined to act at the gut regulatory hormone level. Ninjin-to, Rikkunshi-to, and Dai-kenchu-to affect gastrointestinal motility and based on empirical evidence their effects are assumed to be due to changes in the levels of somatostatin-, motilin-, gastrin-, or VIP-immunoreactive substances (IS) in plasma.14-18) Furthermore, abnormalities of gastrointestinal function is presumed to result from obstruction of the autonomic nervous system and changes in hormone levels. Thus we examined the plasma levels of gut regulatory peptides (somatostatin, motilin, gastrin, and VIP).Radioimmunoassays (RIA) to detect motilin have been developed by several groups using 125 I-motilin. [19][20][21] However, in terms of safety, sensitivity, and ease of handling, RIA methods are still less than satisfactory. We developed a sensitive and specific double-antibody enzyme immunoassay (EIA) for detecting motilin, using motilin-linked b-D-galactosidase as a marker antigen, a secondary antibody-coated immunoplate, and 4-methylumbelliferyl-b-D-galactopyranoside as a fluorogenic substrate.The purpose of this...

Rikkunshi-to, a traditional Chinese (Kampo) herbal medicine, is prepared from eight crude herbs: Ginseng Radix, Atractylodis Rhizoma, Hoelen, Pinelliae Tuber, Aurantii Nobilis Pericarpium, Zizyphi Fructus, Glycyrrhizae Radix, and Zingiberis Rhizoma. This medicine was evaluated for its clinical usefulness in the treatment of chronic hypofunctions of gastrointestinal tract including gastric flatulence, anorexia, nausea, and vomiting. Recently, those effects of Rikkunshi-to were proved to be based on increased blood flow to the stomach, accelerated gastric emptying, and improved gastric mucosal damage. 1-3)In recent reports, some Chinese herbal medicines used to treat those experiential gastrointestinal effects have been elucidated from the viewpoint of gut-regulated hormone levels. Among the medicines, Ninjin-to and Dai-kenchu-to regulated gastrointestinal motility. One of the factors of those effects was assumed to be due to causing increases in the levels of somatostatin, motilin, gastrin, and VIP (vasoactive intestinal peptide) in plasma. [4][5][6][7] Furthermore, the abnormality of gastrointestinal motility of non-ulcer dyspepsia as an indication of Rikkunshi-to was presumed to be caused by the obstruction of the automatic nervous system and by abnormal hormone levels.8) Therefore, we examined the plasma levels of gut-regulated peptides (somatostatin, motilin, gastrin, and VIP).Somatostatin acts as an inhibitor of hormone release. It participates in regulating gastrointestinal motility with motilin. [9][10][11][12][13][14] Motilin has powerful fundic pouch motor-stimulating activity, 15) and is one of the most important factors controlling the regular occurrence of phase-3 contractions of the migrating motor complex (MMC). 16,17) Gastrin stimulates acid secretion and gastrin release is mediated by various mechanisms.18) VIP is widely distributed in the central and peripheral nervous system. 19) This peptide has a vasodilating effect and is an important neurotransmitter for the enteric nervous system. [20][21][22] The purpose of this study was to determine the effects of Rikkunshi-to on the plasma levels of somatostatin-, motilin-, gastrin-, and VIP-immunoreactive substances (IS) in healthy subjects. MATERIALS AND METHODSMaterials Rikkunshi-to (EK-43, lot. 26L99), prepared as a 4.1 g dried powder extract in the following proportions: Ginseng Radix (4.0 g), Atractylodis Rhizoma (4.0 g), Hoelen (4.0 g), Pinelliae Tuber (4.0 g), Aurantii Nobilis Pericarpium (2.0 g), Zizyphi Fructus (2.0 g), Glycyrrhizae Radix (1.0 g), and Zingiberis Rhizoma (0.5 g), was kindly supplied by Kanebo Co., Ltd. (Tokyo, Japan). An additive, consisting of EK-43, was used as a placebo. Synthetic somatostatin, porcine motilin, human gastrin I (G17), and VIP were purchased from Peptide Institute, Inc. (Osaka, Japan). An antiserum to somatostatin was purchased from Cambridge Res. Biochem. (Cambridge, U.K.). Antisera to motilin (A602/ R1B), gastrin (A600/R1B), and VIP (A604/R1B) were purchased from Biogenesis, Ltd. (Poole, U.K.). All other rea...

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