The effects of hepatic transit on concentrations of synthetic cyclic (ovine) somatostatin and of highly purified (porcine) vasoactive intestinal peptide were studied in five conscious dogs prepared with indwelling portal catheters. The peptides were infused via peripheral vein catheters or the portal catheters for 40 minutes at actual integrated doses of 2.8 pmol/kg/min for vasoactive intestinal peptide an 8.2 pmol/kg/min for somatostatin. Specific radioimmunoassays were used for the measurement of the circulating peptides. As estimated from the plateau peptide concentrations achieved a hindleg vein during the portal and the peripheral infusions, the transhepatic loss of immunoreactive vasoactive intestinal peptide was 72.9 +/- 2.1%, against 27.5 +/- 12.5% for somatostatin. For the given doses of peptides infused systematically, the half-life, metabolic clearance rate, and distribution volume were, respectively, 1.80 +/- 0.1 minutes, 39.3 +/- 5.2 ml/kg/min, and 103.7 +/- 14.8 ml/kg for vasoactive intestinal peptide, and 1.0 +/- 0.2 minutes, 95.2 +/- 12.5 ml/kg/min, and 114.7 +/- 6.0 ml/kg for somatostatin. These results indicate that (ovine) somatostatin and (porcine) vasoactive intestinal peptide are both readily cleared from plasma in dogs. In the present experimental conditions, vasoactive intestinal peptide, but not somatostatin, was rapidly altered through hepatic transit so that it escaped recognition by the assay system.
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