Liver uptake of trypsin-inhibitor complexes; differences between suckling and adult rats.
Previous studies have demonstrated increased intestinal trypsin uptake in newborn rats compared to adults. The mechanisms that protect tissues against proteolytic damage by trypsin include trypsin-inhibitor binding and subsequent liver uptake. In order to examine these mechanisms, bovine trypsin (1.25 mg/100 g body weight) plus trace 125I-trypsin were injected into the portal vein of 2-week-old and adult rats. Liver, kidney and plasma 125I activity were assessed at 1, 5 or 15 min following infusion and the different trypsin inhibitor fractions were separated and examined for 125I activity. Newborn rats had significantly increased plasma levels of 125I-trypsin and significantly decreased liver 125I levels 1 min after infusion compared to adults. In addition, the slow decline in liver 125I activity seen in the adult rats did not occur in the newborns. The pattern of trypsin-inhibitor binding was not significantly different at 1, 5 and 15 min and there were no differences at these time intervals between newborns and adults. We suggest that the newborn liver is less effective in clearing infused trypsin leading to increased plasma levels, and this increased plasma trypsin concentration subsequently leads to increased liver levels of 125I-trypsin. The increased trypsin levels in the liver may predispose newborns to protease-induced liver damage.
Levine
J J
JJ
Department of Pediatric Gastroenterology/Nutrition, Schneider Children's Hospital, Albert Einstein College of Medicine, New Hyde Park, N.Y.
Pettei
M J
MJ
D000209:Acute-Phase Proteins; D000375:Aging / Q000502:physiology*; D000818:Animals; D000833:Animals, Suckling / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D011480:Protease Inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014357:Trypsin / Q000378:metabolism* / Q000493:pharmacokinetics; D000515:alpha 1-Antitrypsin / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
D000209:Acute-Phase Proteins; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; C017894:alpha 1-inhibitor 3; D000511:alpha-Macroglobulins; D014357:Trypsin