AJP - Gastrointestinal and Liver Physiology, Vol 246, Issue 3 226-G234, Copyright © 1984 by American Physiological Society
Somatostatin metabolism: differences in clearance of N-terminal and central portions of molecule during perfusion of rat liver
H. S. Sacks, L. C. Terry, R. K. Wright and F. B. Stentz
Clearance of cyclic somatostatin (SRIF) from a plasma-free recirculating
medium containing human erythrocytes and a bovine albumin fraction was
measured with site-specific N-terminal (sheep B) and central core-directed
(R101) radioimmunoassays during perfusion of the isolated rat liver (3-4
g). With the N-terminal radioimmunoassay (RIA), the t 1/2, hepatic
clearance, and extraction of somatostatinlike immunoreactivity (SLI) were
20.9 +/- 2.0 (SE) min, 2.82 +/- 0.27 ml/min, and 35.2 +/- 3.4%.
Corresponding values for the centrally directed assay were 51.0 +/- 6.3
min, 1.16 +/- 0.14 ml/min, and 14.4 +/- 1.8%. Clearances of
immunoprecipitable 125I-Tyr-SRIF and [125I-Tyr11]SRIF were 6.56 and 1.06
ml/min, respectively, and were not saturable by 1 microM Tyr-SRIF and SRIF,
respectively. SRIF (1.26 +/- 0.09 nM) and SRIF-28 (1.34 +/- 0.14 nM)
clearances determined by R101 RIA were similar. After SRIF-28 perfusion,
high-performance liquid chromatographic analysis of SLI showed 86% to be
retained with the SRIF-28 peak and 14% with the SRIF peak, suggesting no
major conversion of SRIF-28 to SRIF. Des-(Ala1,Gly2)-N3-Ac-SRIF and
dihydrosomatostatin were cleared more rapidly than SRIF. Clearance of SLI
by the perfusate without the liver was 12-43% of liver clearance, depending
on the peptide examined. These results support the hypothesis that
aminopeptidase and endopeptidase activities are involved in SRIF clearance
by the intact liver. The activities appear to function independently. The
intrachain disulfide bond of SRIF may confer relative stability during its
hepatic metabolism.
