Stimulation of gastric secretion and enhanced gastric mucosal damage following central administration of pancreatic polypeptide (PP) in rats.
The present study was carried out to investigate the central effects of pancreatic polypeptide on gastric secretion and gastric ulcer formation in conscious rats. Intracisternal injection of rat pancreatic polypeptide (62.5, 250, and 1000 ng/rat) into pylorus-ligated rats resulted in a dose-dependent stimulation of gastric acid and pepsin secretion. In contrast, intraperitoneal injection of even higher doses of pancreatic polypeptide (250, 1000, and 2500 ng/rat) failed to increase gastric secretion. This stimulatory effect of centrally administered pancreatic polypeptide was completely blocked by vagotomy and by pretreatment with atropine. Intracisternal injection of PP (500-2000 ng/rat) dose-dependently increased the severity of gastric lesions induced by 2-deoxy-D-glucose or indomethacin. In contrast, intraperitoneal injection of PP failed to increase the severity of the gastric lesions induced by 2-deoxy-D-glucose or indomethacin. These results indicate that pancreatic polypeptide is capable of acting centrally in the brain to stimulate gastric acid and pepsin secretion through a vagal, muscarinic pathway and in so doing exerts an ulcerogenic action on the gastric mucosa.
Okumura
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Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Pappas
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Taylor
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D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003847:Deoxyglucose / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity; D008297:Male; D010191:Pancreatic Polypeptide / Q000494:pharmacology* / Q000633:toxicity; D010434:Pepsin A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D014628:Vagotomy
D010191:Pancreatic Polypeptide; D001285:Atropine; D003847:Deoxyglucose; D010434:Pepsin A; D007213:Indomethacin