Inhibition of gastric acid secretion in rats and in dogs by corticotropin-releasing factor

Abstract

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 pentagastrinstimulaled gastric acid output at intravenous doses of 4–17 nmol · kg−1 · h−1 in urethane-anesthetized, gastric fistula rats and at 0.1–1-nmol · kg−1 · h−1 doses in conscious, gastric-fistula dogs. The inhibitory effect of corticotropin-releasing factor was dosedependent, 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 · kg−1 · h−1, did not modify gastric acid secretion stimulated by pentogastrin 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 corticotropinreleasing 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.