Effect of transforming growth factor-alpha on gastric acid secretion in rats and monkeys.
The effect of transforming growth factor-alpha was studied in histamine-stimulated gastric acid secretion in monkeys and in pylorus-ligated rats. In monkeys, transforming growth factor-alpha given intravenously in a stepwise manner gradually reduced gastric acid secretion. A dose of 0.1 mmol/kg induced about a 50% inhibition of gastric acid output, while about 100% inhibition of the same parameter, was observed after a dose of 1 nmol/kg. Following a single administration of 1 nmol/kg intravenously in monkey, the maximum inhibitory effect on gastric acid output was reached 60 min after the administration of the drug, when a 91.8% inhibition was observed. Pretreatment values were reached 210-240 min after transforming growth factor-alpha administration. In pylorus-ligated rats, transforming growth factor-alpha, at doses of 9 and 18 nmol/kg produced an almost complete inhibition of gastric acid secretion. In this model, the ED50 was calculated to be 4.5 nmol/kg. Comparison with epidermal growth factor on the same models of gastric acid secretion showed that these two compounds have similar inhibitory potency. However, the effect of transforming growth factor-alpha on gastric acid secretion in monkeys was shorter lasting than that of epidermal growth factor.
Guglietta
A
A
Department of Experimental Therapy, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Lesch
C A
CA
Romano
M
M
McClure
R W
RW
Coffey
R J
RJ
D000818:Animals; D000863:Antacids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D000863:Antacids; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor