Enzyme Immunoassay of Motilin in Human Plasma.

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We examined the effects of the histamine H 2 -receptor antagonist, lafutidine, on the levels of gastrointestinal peptides (somatostatin, calcitonin gene-related peptide (CGRP), gastrin, secretin, and motilin) in plasma from healthy subjects. After a single oral administration of lafutidine (10 mg), the plasma lafutidine level (186؎ 13.4 ng/ml) was highest in the 60-min sample after administration and then the plasma level fell. Lafutidine caused significant increase in plasma somatostatin levels at 20 to 120 min and in CGRP levels at 40 to 120 min, compared with a placebo group. The physiological release of plasma secretin was reduced by administration of lafutidine, but the medicine did not alter the level of gastrin or motilin. These results suggest that the pharmacological effects of lafutidine on regulation of gastrointestinal functions closely relate to changes of somatostatin-, CGRP-and secretin-immunoreactive substance levels in human plasma.

Section: Preparation Of Plasma Extractsmentioning

confidence: 99%

Lafutidine Changes Levels of Somatostatin, Calcitonin Gene-Related Peptide, and Secretin in Human Plasma

Naito¹,

Takeyama²

2002

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“…19) Antiserum (Y121) was obtained from Peptide Institute, Inc. (Osaka, Japan). Motilin was labeled with b-Dgalactosidase (Boehringer Mannheim Corp., Mannheim, Germany).…”

Section: Preparation Of Plasma Extractsmentioning

confidence: 99%

Effects of Domperidone on Human Plasma Levels of Motilin, Somatostatin, Gastrin, Adrenocorticotropic Hormone and Cortisol

Katagiri

Ikawa

Takeyama

2005

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Domperidone is an antinauseant and gastrokinetic drug which has been reported to be effective for treating functional gastrointestinal disorders such as dyspepsia, gastroesophageal reflux, nausea and vomiting. Domperidone also has recently been evaluated for its clinical usefulness in stress and depression. This medicine has frequently been used in the treatment of chronic hypofunction of the gastrointestinal system. 1,2) Some patients who take this medicine do not have organic diseases such as peptic ulcer, reflex esophagitis, and gastric cancer but have conditions classified as non-ulcer dyspepsia (NUD). Most NUD patients tend toward depressive and psychosomatic conditions and are exposed to continual affective stress.3) This continual stress causes abnormalities in the hypothalamo-pituitary-adrenal (HPA) axis and autonomic nervous function. 4,5) Some abnormalities of gastrointestinal function are presumed to result from changes in hormone levels. However, the mechanism is not clear.The gastrointestinal peptide motilin is found in specific endocrine cells of the upper small intestine of hogs.6) This peptide strongly stimulates fundic pouch activity 7) and plays an important physiological role in intestinal contractility, particularly in the fundus and antral of the pouch of the stomach. It is one of the most important factors controlling the regular occurrence of phase III interdigestive migrating contractions. 8,9) Somatostatin is present in high amounts in the stomach. 10)This peptide inhibits the secretion of motilin and gastrin, and it also inhibits gastric, duodenal, and biliary motility. 11)Gastrin was first detected in extracts of pyloric antral mucosa.12) The most potent actions of gastrin are the stimulation of both gastric acid secretion and antral motility. 13)Adrenocorticotropic hormone immunoreactive substances (ACTH-IS) are found in tissues other than the pituitary gland (i.e. brain, adrenal gland, gastrointestinal tract, pancreas, thyroid gland, and placenta). The secretion of ACTH is affected by mechanisms of circadian rhythm and negative feedback by blood cortisol, and neurogenic stimulation.14) Plasma levels of ACTH increase under stress and the peptide has the secretomotory action of glucocorticoid. 4) Cortisol, commonly used to indicate the level of stress, is secreted by the zona fasciculate of the adrenal cortex and its secretion is dependent on the ACTH level.In general, venipuncture for blood sampling is believed to be a stress factor that can increase circulating levels of ACTH, cortisol, and other substances. 15,16) Repetitive blood sampling places subjects under artificial stress, and venipuncture as a stressor is useful for evaluation of the pharmacological effects of drug. 17)The purpose of this study was to determine the effects of domperidone on plasma levels of motilin-IS, somatostatin-IS, gastrin-IS, ACTH-IS, and cortisol in healthy individuals. MATERIALS AND METHODS SubjectsFive healthy male volunteers, aged 25-31 (median 28) years and weighing 54-70 (median 65.1) kg, particip...

“…Enzyme Immunoassay for Somatostatin-, Motilin-, Gastrin-, and VIP-IS Peptide levels in plasma were measured using a highly sensitive enzyme immunoassay for somatostatin-, 23) motilin-, 24) gastrin-, 25) and VIP-IS 26) as previously described. The assay was performed by a delayed addition method.…”

Section: Preparation Of Plasma Extractsmentioning

confidence: 99%

Rikkunshi-to Raises Levels of Somatostatin and Gastrin in Human Plasma.

Naito

Yasunaga

Takeyama

2001

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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...