Role of Liver and Intestines in the Degradation of Epidermal Growth Factor

Abstract

Epidermal growth factor (EGF) is widely distributed in the gastrointestinal tissues and released into the gut lumen but its physiological role is questionable because of the postulated high uptake and degradation of this peptide in the liver. This study was designed to examine the action of EGF administered intraduodenally (i.d.), intravenously (i.v.) or intraportally (i.p.) on pentagastrin-stimulated gastric and pancreatic secretion and to determine the role of liver in the EGF uptake. In conscious dogs with gastric and pancreatic fistulas, EGF infused i.v. or i.p. in graded doses (0.12-1.0 microgram/kg.h) caused a dose-dependent inhibition of pentagastrin-induced gastric H+ secretion without alteration in pancreatic protein secretion. EGF infused i.v. and i.p. raised significantly plasma levels of the peptide but these increments were significantly lower with i.p. than with i.v. infusion. EGF given i.d. did not affect gastric or pancreatic secretion and failed to raise significantly plasma EGF level. In anesthetized dogs, no difference was found in the basal plasma EGF levels between arterial and portal or hepatic blood. during i.v. infusion of EGF, plasma EGF level in hepatic venous blood was about 40% lower and that in the portal blood was about 30% lower than that in arterial blood indicating a marked uptake of peptide during the passage through the liver and the intestines, respectively. EGF was present in negligible amounts in gastric secretion but appeared in nanogram concentrations in the pancreatic secretion and increased after pentagastrin stimulation. We conclude that (1) the liver and the intestines are almost equally involved in partial degradation of EGF and that the kidneys may also contribute to the elimination of circulating EGF; (2) the uptake of EGF by these organs is limited and can be overcome by increasing doses of infused EGF, and (3) absorption of EGF from the intestinal lumen does not contribute to its circulating concentrations.