Hepatic clearance of somatostatin and gastrin-releasing peptide

In order to examine hepatic clearance of gastrointestinal regulatory peptides, rat livers were perfused in situ, and radiolabelled somatostatin (S-14, S-28), gastrin-releasing peptide (GRP-14, GRP-27), and vasoactive intestinal peptide (VIP) were injected into the portal vein and hepatic venous effluent was collected. S-14 and S-28 were not affected significantly by hepatic transit: 91.6 +/- 2.8% (SEM) of S-14 and 95.9 +/- 2.2% of S-28 were recovered, and neither peptide was degraded by hepatic transit, as determined by immunoprecipitation and gel chromatography. GRP-14 and GRP-27 were also not affected by hepatic transit: 91.5 +/- 1.6% of GRP-14 and 94.4 +/- 2.4% of GRP-27 were recovered intact. In contrast, when radiolabelled VIP was infused into the portal vein, 56.7 +/- 7.4% of injected labelled VIP appeared in the hepatic venous effluent, of which only 33.5 +/- 1.2% was intact peptide. Results of these studies indicate that enteric VIP released into the splanchnic/portal circulation is cleared by hepatic transit. However, somatostatin and GRP peptides appear to traverse the liver intact and could potentially produce systemic biological effects.