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J.Health Sci., 51(3), 294-299, 2005
Lansoprazole Raises Somatostatin, Calcitonin Gene-Related Peptide, and Substance P Levels in Healthy Human Plasma
Fumihiko Katagiri,* Shin Inoue, Yuhki Sato, Hiroki Itoh, and Masaharu Takeyama
Department of Clinical Pharmacy, Oita University Hospital, 1-1, Idaigaoka, Hasama-machi, Oita 879-5593, Japan
Lansoprazole, a proton pump inhibitor (PPI), is widely used in the treatment of peptic ulcer, gastroesophageal reflux disease and eradication of Helicobacter pylori. Lansoprazole has been reported to be a PPI with mucosal protective action. However, except for inhibition of gastric acid secretion, its mechanism of action is not well understood. We therefore examined the effects of lansoprazole on plasma levels of gastrointestinal peptides (gastrin, somatostatin, motilin, vasoactive intestinal peptide [VIP], substance P, and calcitonin gene-related peptide [CGRP]). Lansoprazole 30 mg or placebo was orally administered to five healthy male volunteers aged 25-30 years. Venous blood samples were taken before and 30, 60, 90, 120, 180, 240, and 360 min after administration. Plasma peptide levels were measured using a sensitive enzyme immunoassay. Compared with the response of the placebo treated group, lansoprazole caused significant (p < 0.05) increases in somatostatin-, VIP-, substance P- and CGRP-like immunoreactive substance (IS) levels at 120, 120, 90-240, and 120 min, respectively. Furthermore, lansoprazole significantly suppressed temporary elevation (30 min) of placebo gastrin-IS levels. But lansoprazole had no effect on plasma motilin-IS levels compared with the placebo. In this study, lansoprazole raised somatostatin-IS levels and inhibited the increase in gastrin-IS levels. On the other hand, lansoprazole raised substance P- and CGRP-IS levels. Recently, capsaicin-sensitive afferent nerves have been shown to play an important role in gastric mucosal defensive mechanisms. Capsaicin stimulates afferent nerves and enhances the release of CGRP and substance P in the stomach. We hypothesize that lansoprazole might not only potently inhibit gastric acid secretion but also exert gastroprotective actions via capsaicin-sensitive afferent nerves.
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