gastrins and plaunotol

Recently, we have reported that several nonacid agents including phenylpentol, methanol extract of licorice root (FM 100), plaunotol, and teprenon stimulate release of endogenous secretin in humans, dogs, and rats. The latter three are antiulcer agents developed in Japan that have a protective effect on the gastric mucosa. We have clearly shown that plaunotol inhibits postprandial gastrin release and gastric acid secretion that parallel the increase in plasma secretin concentration. It has also been recently demonstrated that the secretin-induced inhibition of gastric acid secretion in rats is completely blocked by indomethacin, a potent inhibitor of prostaglandin synthesis. It appears that the inhibitory action of secretin on gastric acid secretion is mediated mainly by endogenous prostaglandins. Because the three antiulcer agents FM 100, plaunotol, and teprenon have been shown to increase the content of endogenous prostaglandins in the gastric mucosa, endogenous secretin released by these agents may play a significant role in their mucosal protective action. It is concluded that the antiulcer effect of these drugs could in part be attributable to their unique ability to release endogenous secretin, and that secretin is a potential mediator of the antiulcer actions of mucosal protective agents.

Topics: Animals; Anti-Ulcer Agents; Cimetidine; Diterpenes; Fatty Alcohols; Food; Gastric Acid; Gastrins; Humans; Prostaglandins; Ranitidine; Rats; Secretin

The aim of the present study was to examine the efficacy and safety of combination therapy with amoxicillin (AMPC), lansoprazole, and plaunotol for the eradication of H. pylori in dialysis patients. The subjects consisted of 15 dialysis patients (10 men and 5 women, mean age of 56 +/- 2.4 years) in whom H. pylori was found in the stomach. H. pylori status was evaluated by histology, culture and rapid urease test with biopsy specimens of the gastric mucosa. The patients were treated with AMPC 500 mg once a day for 3 weeks, lansoprazole 30 mg once a day for 8 weeks and plaunotol 80 mg three times a day for 24 weeks. In addition, the concentrations of serum gastrin and gastric juice ammonia were measured. Fourteen patients completed the treatment schedule, while one discontinued treatment because of nausea and diarrhea. Among the 14 patients, H. pylori was eradicated in 11 without any side effects (eradication rate 78.6%). Concentrations of gastric juice ammonia and serum gastrin were reduced significantly in patients who became H. pylori-negative. The present study indicates that combination therapy with AMPC, lansoprazole and plaunotol is safe and efficient for the eradication of H. pylori in dialysis patients. The results also suggested that elevated concentrations of gastric juice ammonia and serum gastrin in dialysis patients can be attributed, at least in part, to H. pylori infection.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Ammonia; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Diterpenes; Drug Therapy, Combination; Fatty Alcohols; Female; Gastric Juice; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Middle Aged; Omeprazole; Penicillins; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

Omeprazole markedly inhibits basal and stimulated gastric acid secretion and has the ability to produce hypergastrinemia and hyperplasia of enterochromaffin-like cells in humans. On the other hand, plaunotol, an acyclic diterpene alcohol, has been reported to inhibit gastrin release by stimulating endogenous secretion release. We investigated the effect of plaunotol on serum gastrin levels after six to eight weeks of omeprazole (20 mg/day) administration in 22 patients (16 males, 6 females; mean age 52.3, range 36-70 years) with peptic ulcer disease. The patients were randomized to the following two groups: 11 subjects with omerprazole alone (single group) and 11 with omeprazole plus plaunotol (240 mg/day) (combination group) treatment. There were no significant differences between the two groups concerning age, sex, ulcer stage, ulcer history, environmental factors, and Helicobacter pylori (HP) prevalence. After complete drug(s) administration, serum immunoreactive (ir) -gastrin levels increased significantly in the single group (P < 0.001) in contrast to the combination group, and plaunotol significantly inhibited hypergastrinemia induced by omeprazole administration (P < 0.001). Significant increases in serum ir-calcitonin gene-related peptide concentrations were observed in the combination group compared to the single group (P < 0.05). However, there were no significant changes in sereum ir-secretin, somatostatin, and vasoactive intestinal polypeptide levels as well as ulcer healing and HP prevalence between the two groups. These findings suggest that plaunotol may suppress hypergastrinemia induced by long-term omeprazole administration, at least partly, via a certain brain-gut hormone affecting gastrin release.

Topics: Adult; Aged; Anti-Ulcer Agents; Diterpenes; Fatty Alcohols; Female; Gastrins; Gastrointestinal Hormones; Humans; Male; Middle Aged; Omeprazole; Peptic Ulcer

Plaunotol, an acrylic diterpene alcohol, is a new antiulcer agent derived from the "plau-noi" plant and has been reported to stimulate the release of endogenous secretin in humans. We investigated the effect of plaunotol on postprandial gastrin release, comparing it to the effect of exogenous secretin in a physiological dose in eight healthy volunteers. Four sets of experiments were performed in each volunteer: (1) meal alone, (2) meal after intravenous ranitidine (50 mg), (3) meal after oral administration of plaunotol (320 mg) in addition to ranitidine, and (4) meal after ranitidine with simultaneous intravenous infusion of secretin (0.03 CU/kg/hr). The postprandial increase in plasma secretin concentration was significantly reduced by ranitidine, while postprandial gastrin release was markedly exaggerated. Plaunotol in combination with ranitidine significantly increased secretin release and inhibited gastrin release after a meal. Intravenous infusion of secretin resulted in significant suppression of postprandial gastrin release exaggerated by ranitidine. The present study indicates that plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action.

Topics: Adult; Anti-Ulcer Agents; Diterpenes; Fatty Alcohols; Female; Food; Gastrins; Humans; Male; Ranitidine; Secretin