Peripheral acid inhibitory action of corticotropin releasing factor: mediation by nongastric mechanisms.
Corticotropin releasing factor (CRF) inhibits gastric acid secretion via both central neural and peripheral mechanisms. We examined whether local gastric factors may mediate the peripheral action of CRF. In pylorus-ligated anesthetized rats, CRF infusion (15 nmol/kg X h) produced roughly 60% inhibition of pentagastrin (16 micrograms/kg X h)-stimulated acid secretion. Similarly, in the gastric fistula dog, CRF (1 nmol/kg X h) inhibited pentagastrin-induced acid secretion by 74%. This action of CRF did not result from direct inhibition of gastric parietal cells, as concentrations of the peptide ranging from 10(-11) to 10(-6) M had no effect on the activity of isolated parietal cells in the unstimulated state or after stimulation with pentagastrin (10(-8) M), histamine (10(-5) M), or carbachol (10(-5) M), against a background of isobutylmethylxanthine (10(-4) M). To determine whether local hormones may mediate CRF-induced acid inhibition, we examined the peptide's effect on the release of somatostatin and gastrin from cultured canine gastric D and G cells and from isolated perfused rat stomachs. Corticotropin releasing factor in doses ranging from 10(-11) to 10(-6) M had no influence on release of either gastric peptide under basal conditions or after stimulation of gastrin with carbachol (10(-6) M) and somatostatin with isoproterenol (10(-8) M). These data suggest that the peripheral acid inhibitory action of CFR is mediated by nongastric mechanisms.
D000818:Animals; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003864:Depression, Chemical; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000032:analysis; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D005755:Gastrins; D003346:Corticotropin-Releasing Hormone