Shin Inoue

Effects of Itopride Hydrochloride on Plasma Gut-Regulatory Peptide and Stress-Related Hormone Levels in Healthy Human Subjects

Itopride hydrochloride (itopride), a gastrokinetic drug, has recently been evaluated for its clinical usefulness in functional dyspepsia. We investigated effects of itopride on human plasma gastrin-, somatostatin-, motilin-, and cholecystokinin (CCK)-like immunoreactive substances (IS); adrenocorticotropic hormone (ACTH)-immunoreactive substances (IS), and cortisol under stress conditions in healthy subjects. A single administration of itopride caused significant increases in plasma somatostatin- and motilin-IS levels compared to placebo. Itopride significantly decreased plasma CCK-IS, and suppressed the ACTH-IS level compared to placebo. We hypothesize that itopride may have an accelerating gastric emptying effect, and a modulatory effect on the hypothalamo-pituitary-adrenal axis and autonomic nervous functions. These effects might be beneficial in stress-related diseases, suggesting that itopride has clinicopharmacological activities.

Ecabet sodium raises plasma levels of calcitonin gene‐related peptide and substance P in healthy humans

Ecabet sodium (ecabet), a cytoprotective drug, produces an increase in mucosal blood flow. One of the gastrointestinal motility regulatory factors has been assumed to be the induction of changes in the levels of peptides (gastrin, somatostatin and motilin) in plasma. On the other hand, recently, capsaicin‐sensitive afferent nerves were shown to play an important role in gastric mucosal defensive mechanism. Capsaicin stimulates afferent nerves and enhances the release of calcitonin gene‐related peptide (CGRP) and substance P in the stomach. We studied the effect of ecabet on human plasma gastrin‐, somatostatin‐, motilin‐, CGRP‐ and substance P‐like immunoreactive substance (IS) in healthy subjects. Ecabet sodium at a dose of 3.0 g, or placebo, was orally administered in five healthy males. The blood samples were taken before and at 20, 40, 60, 90, 120, 180 and 240 min after administration, subjected to extracting procedures, and submitted to a highly sensitive enzyme immunoassay system. Single administration of ecabet caused significant (P < 0.05) increases in plasma CGRP‐, substance P‐ and somatostatin‐IS concentration compared with placebo. Ecabet significantly decreased plasma gastrin‐IS levels compared with placebo. In this study, we hypothesized that ecabet might stimulate capsaicin‐sensitive afferent nerves indirectly and improve mucosal blood flow; this might be a key mechanism underlying its gastroprotective action.

PI-4The effects of itopride on plasma gut-regulatory peprides and stress-related hormones levels in healthy humans

Itopride, a gastrokinetic drug with anti‐dopamine and anti‐acetylcholinesterase activity, has recently been evaluated for its clinical usefulness in non‐ulcer dyspepsia that is closely related to stress. Here, we studied the effects of itopride on human plasma gastrin‐, somatostatin‐, motilin‐ and CCK‐like immunoreactive substance (IS), and ACTH‐IS and cortisol under stress conditions using repetitive blood sampling in healthy subjects.

Effect of gastrointestinal function regulatory Kampo medicine, Dai‐kenchu‐to on human plasma calcitonine gene‐related peptide, substance P and somatostatin levels

Traditional Chinese herbal (Kampo) medicines, Dai‐kenchu‐to (DKCT) have been frequently used in the empirical treatment of gastrointestinal obstructions. Although it has been already reported that DKCT increases in the plasma levels of gastrointestinal peptides {vasoactive intestinal polypeptides (VIP) and motilin}, which improves feelings of abdominal coldness and gastrointestinal motility, the mechanism is not yet well understood. In this study, we examined effects of DKCT on the plasma calcitonine gene‐related peptide (CGRP), substance P (SP) and somatostatin (SS) levels.

Ecabet raises calcitonin-gene related peptide and substance P in human plasma

Ecabet, an antiulcer drug, has gastric protective effects that are improvement of blood flow or promotion of bicarbonate secretion. Recently, capsaicin sensitive afferent nerves play an important role in gastric mucosal defensive mechanism. Capsaicin stimulates afferent nerves and enhances the release of calcitonine gene‐related peptide (CGRP) and substance P in the stomach. We studied the effect of ecabet on human plasma CGRP and substance P in healthy subjects.

Effect of omeprazole on brain‐gut peptides concentrations in human plasma

Omeprazole, proton pump inhibitor, is widely used in treatment of peptic ulcer, Gastro esophageal reflux disease and eradication of Helicobacter pylori. But the mechanism is not well understood. So we examined the effects of omeprazole on plasma levels of gastrointestinal peptides {somatostatin, gastrin, motilin, vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene related peptide (CGRP)}. Methods: Omeprazole or placebo was orally administered in five healthy male volunteers aged 25–30 years. Venous blood samples were taken before and at 30, 60, 90, 120, 180, 240 and 360 min after administration of the drug. Plasma peptide levels were measured using a sensitive enzyme immunoassay. Results: Omeprazole (20mg) causes significant increase in somatostatin‐IS at 60‐240 min compared with the response of the placebo treated group. Furthermore omeprazole showed 35.1 % (60min) increase of placebo motilin levels and 38.5 % (60min) inhibition of placebo gastrin levels. But omeprazole had no effect on plasma VIP‐IS, SP‐IS and CGRP‐IS levels compared with the placebo treated groups. Conclusions: In this study, omeprazole enhanced somatostatin‐IS levels. Somatostatin, a polypeptide, which distributes widely in the gastrointestinal tract, participates in the control of gut motility and hormones secretion. Omeprazole might have pharmacological mechanism not only inhibition of gastric acid secretion but also regulation of gastrointestinal peptide.