Hepatic clearance of rat plasma intestinal alkaline phosphatase

G. P. Young, I. S. Rose, Simon Cropper, Shakuntla Seetharam, David H. Alpers

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The mechanism and route of clearance of intestinal alkaline phosphatase from plasma have been studied in rats to define the magnitude of hepatic extraction and biliary excretion of the enzyme. Plasma clearance, tissue distribution, and biliary excretion of enzyme were followed after intravenous administration of physiological amounts of 125I-labeled rat intestinal alkaline phosphatase. The plasma disappearance curve was biphasic; the initial phase was rapid, during which 50% of injected enzyme was selectively extracted by the liver over 5 min. Less than 4% of total hepatic radioactivity was excreted into bile over 80 min; this was shown by chromatographic analysis to be degraded enzyme only. Rapid clearance of enzyme could be significantly slowed by injection of large amounts of mannan or N-acetylglucosamine-bovine serum albumin, but not by desialylated fetuin, demonstrating that clearance was probably mediated by mannose/N-acetylglucosamine-specific receptors. It is concluded that, under physiological conditions, rat plasma intestinal alkaline phosphatase is rapidly cleared from the circulation by the liver. However, biliary excretion of undegraded enzyme is negligible, and a physiologically significant enterohepatic circulation seems most unlikely.

Original languageEnglish
Pages (from-to)G419-G426
Number of pages8
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume247
Issue number4
DOIs
Publication statusPublished - 1 Oct 1984
Externally publishedYes

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