Gastric ECL-cell hyperplasia produces enhanced basal and stimulated gastric acid output but not gastric erosion formation in the rat.
1. The purpose of this study was to examine the change in gastric acid output and gastric erosion formation produced by inducing gastric enterochromaffin-like (ECL) cell hyperplasia in female rats. 2. Rats were treated with vehicle or ranitidine (1,200 mumol/kg/day x 4 wks) administered via SC Alzet minipumps. Experiments were performed 24 hours after removing the minipump, when the inhibitory effect of ranitidine on gastric acid secretion had been lost. 3. Basal gastric acid secretion was 7-fold higher in chronic ranitidine animals than in sham control. 4. Both total and net gastric acid secretions stimulated by carbachol/pentagastrin infusion or histamine injection were significantly higher in the chronic ranitidine animals than in controls. 5. By contrast, intracisternal injection of the chemical vagal stimulant RX77368 (100 ng) resulted in no net increase in acid output of recovered ranitidine-pretreated group. 6. No significant changes in gastric erosions produced experimentally by cold exposure plus restraint or indomethacin pretreatment were noted in recovered chronic ranitidine animals compared to sham controls. 7. These findings suggest that achlorhydria-induced ECL cell hyperplasia augments both basal and stimulated gastric acid secretory function. The histamine results implicate an enhanced parietal cell mass, upregulation of H2 receptors, and/or second-messenger events at the parietal cell as the mechanism for the enhanced gastric secretory response.
LePard
K J
KJ
Department of Physiology, Ohio State University, Columbus, USA.
Mohammed
J R
JR
Stephens
R L
RL
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006632:Histamine / Q000494:pharmacology; D006965:Hyperplasia / Q000139:chemically induced / Q000378:metabolism; D007213:Indomethacin; D010418:Pentagastrin / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011899:Ranitidine / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000209:etiology*; D013312:Stress, Physiological; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology
D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D006632:Histamine; D011899:Ranitidine; D002217:Carbachol; D010418:Pentagastrin; D011761:Pyrrolidonecarboxylic Acid; D007213:Indomethacin