Mechanism of gastric acid hypersecretion in patients with islet cell tumor without hypergastrinemia: studies in rats.
OBJECTIVE
A nongastrin acid-stimulating peptide (NGASP) has been found in ulcerogenic pancreatic tumor syndrome without hypergastrinemia. The mechanism of gastric acid hypersecretion by NGASP was investigated in rats.


METHODS
In vivo, gastric acid secretion and in vitro histamine release from enterochromaffin-like (ECL) cells in responses to tumor extract (TE) and synthetic human gastrin-17 I or pentagastrin (PG) were studied. Whether the 2 secretagogues potentiate each other was determined.


RESULTS
TE dose-dependently stimulated histamine release, which was not blocked by a cholecystokinin (CCK)-B receptor antagonist. When TE was incubated with trypsin, the activity was abolished but was not affected by antibody. However, when rats were pretreated with antigastrin serum or CCK-B receptor antagonist, the acid secretion by TE was virtually abolished. The dose response of acid secretion to TE in the rats receiving PG in a threshold dose was significantly greater than that achieved by TE alone. Similarly, the dose response to PG combined with a threshold dose of TE was significantly greater than that produced by PG alone.


CONCLUSIONS
NGASP stimulates histamine release from ECL cells, but the release is not mediated via CCK-B/gastrin receptor. NGASP and gastrin may potentiate each other to produce acid hypersecretion in ulcerogenic pancreatic tumor syndrome.
Song
Y
Y
Department of Medicine, William B. and Sheila Konar Center For Digestive and Liver Diseases, University of Rochester Medical Center, New York, USA.
Chey
W Y
WY
Chang
T M
TM
Lee
K Y
KY
D007516:Adenoma, Islet Cell / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000502:physiology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D005755:Gastrins / Q000097:blood* / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D014020:Tissue Extracts / Q000494:pharmacology*
D005755:Gastrins; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D014020:Tissue Extracts; C036227:gastrin I; D010418:Pentagastrin