Effect of h-EGF and h-EGF 1-48 on histamine-stimulated gastric acid secretion in rats and monkeys.
The effect of human epidermal growth factor (h-EGF) and its derivative human epidermal growth factor 1-48 (h-EGF 1-48) on histamine-stimulated gastric acid secretion was studied in monkeys and rats. In monkeys, both h-EGF and h-EGF 1-48 given intravenously (i.v.) in a stepwise manner and in doses ranging from 0.01 to 10 nmol/kg, gradually suppressed gastric acid secretion. At the highest dose tested, both compounds essentially abolished gastric acid output. In the same animals, i.v. administration of 1 nmol/kg of h-EGF or h-EGF 1-48 caused an inhibition of gastric acid output that reached a peak at 90 and 60 min after the administration of h-EGF or h-EGF 1-48 respectively. After this maximum gastric inhibitory effect, a gradual return toward pre-injection values was observed. In rats, after subcutaneous (sc) administration, both h-EGF and h-EGF 1-48 dose-dependently inhibited histamine-stimulated gastric acid output as measured 60 min after the administration of the compounds. The maximum inhibitory activity on gastric acid output, observed at a dose of 100 nmol/kg, was 74.4% and 76.0% for h-EGF and h-EGF 1-48 respectively. The same dose of both compounds, however, failed to significantly inhibit gastric acid secretion when administered orally. In all the studies h-EGF 1-48 showed activity and potency comparable to h-EGF.(ABSTRACT TRUNCATED AT 250 WORDS)
Guglietta
A
A
Gastrointestinal Disorders Group, Parke-Davis Pharmaceutical Research Division, Ann Arbor, MI 48105.
Lesch
C A
CA
D000818:Animals; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D008253:Macaca mulatta; D051381:Rats; D017207:Rats, Sprague-Dawley
D004815:Epidermal Growth Factor; D006632:Histamine