Inhibition of gastric acid secretion in rats and in dogs by corticotropin-releasing factor.
Intravenously injected synthetic ovine corticotropin-releasing factor inhibited gastric secretion by reducing gastric secretory volume, acid concentration, and acid output, but elevated plasma gastrin levels in conscious 2-h pylorus-ligated rats. Corticotropin-releasing factor suppressed pentagastrin-stimulated gastric acid output at intravenous doses of 4-17 nmol X kg-1 X h-1 in urethane-anesthetized, gastric fistula rats and at 0.1-1-nmol X kg-1 X h-1 doses in conscious, gastric-fistula dogs. The inhibitory effect of corticotropin-releasing factor was dose-dependent, long-lasting, and reversible. The other newly characterized hypothalamic-hypophysiotropic peptide, growth hormone-releasing factor, hpGRF (1-40), infused at a dose of 18 nmol X kg-1 X h-1, did not modify gastric acid secretion stimulated by pentagastrin in rats. Gastric response to corticotropin-releasing factor in rats was altered neither by naloxone (5 mg/kg i.p.) or indomethacin (10 mg/kg i.p.) pretreatment, nor by hypophysectomy or adrenalectomy, but was partly reversed by vagotomy. These results demonstrate that corticotropin-releasing factor inhibits gastric acid secretion in both rats and dogs. The inhibitory effect of corticotropin-releasing factor on gastric secretion does not require the presence of the pituitary or the adrenal glands, or a functional prostaglandin biosynthetic pathway, and is not mediated through changes in gastrin secretion. It appears to be partially dependent on a degree of vagal tone as well as other mechanisms that await further elucidation.
D000315:Adrenalectomy; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D005755:Gastrins / Q000097:blood; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D007016:Hypophysectomy; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D011708:Pylorus / Q000601:surgery; D051381:Rats; D011919:Rats, Inbred Strains; D014628:Vagotomy
D005755:Gastrins; D005768:Gastrointestinal Hormones; D005749:Gastric Inhibitory Polypeptide; D003346:Corticotropin-Releasing Hormone; D010418:Pentagastrin