Effect of pirenzepine on gastric endocrine cell kinetics during lansoprazole administration.
We studied the effect of pirenzepine on gastric secretion kinetics in rats in a hypochlorhydric state induced by lansoprazole, a proton pump inhibitor. Pirenzepine was administered intramuscularly at a dosage of 20 mg/kg twice daily; and lansorprazole, subcutaneously at 50 mg/kg once daily, both every day for 4 weeks. After the 4-week treatment, serum gastrin and plasma somatostatin levels were determined by radioimmunoassay. In addition, gastrin cells, somatostatin cells, and enterochromaffin-like cells were immunostained and counted. Serum gastrin levels were elevated, and gastrin and enterochromaffin-like cell numbers increased in the group on lansoprazole alone, compared with these values in the control group (which received distilled water). In the group on the lansoprazole and pirenzepine combination, serum gastrin levels decreased, and gastrin and enterochromaffin-like cell numbers were significantly decreased, compared with the respective variables in the group on lansoprazole alone, while the number of somatostatin cells increased in the group on the combination. Plasma somatostatin levels did not vary significantly in any group. It was thus demonstrated that pirenzepine corrects the abnormal gastric secretion kinetics resulting from treatment with lansoprazole alone, such as hypergastrinemia and gastrin and enterochromaffin-like cell hyperplasia.
Omura
N
N
Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
Kashiwagi
H
H
Gang
C
C
Omura
K
K
Aoki
T
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004759:Enterochromaffin Cells / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D019863:Gastrin-Secreting Cells / Q000187:drug effects; D005755:Gastrins / Q000097:blood*; D007700:Kinetics; D064747:Lansoprazole; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000097:blood*; D019864:Somatostatin-Secreting Cells / Q000187:drug effects
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D005755:Gastrins; D018727:Muscarinic Antagonists; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D010890:Pirenzepine; D013004:Somatostatin; D009853:Omeprazole