Somatostatin 28: Comparison with somatostatin 14 for plasma kinetics and low-dose effects on the exocrine pancreas in dogs

The plasma kinetics of the synthetic tetradecapeptide somatostatin and of the newly characterized somatostatin 28 were comparatively assessed in dogs, using a radioimmunoassay system in which both peptides are equally recognized. The metabolic clearance rate, distribution volume, and calculated half-life were 157.0 ± 34.9 ml kg−1 · min−1, 301 ± 76.6 ml/kg and 1.34 ± 0.07 min for the tetradecapeptide infused at progressively increasing doses of 242–2424 pmol kg−1 · h−1, against 28.1 ± 7.5 ml kg−1 · min−1 (p < 0.02), 165 ± 76.4 ml/kg (p > 0.02) and 3.64 ± 0.98 min (p < 0.02) for somatostatin 28 infused at doses of 25–126 pmol kg−1 · h−1. Gel filtration of peripheral plasma sampled while infusing the largest dose of each peptide showed that for periods up to 40 min, there was no evidence of conversion into the opposite form. When administered intravenously for 1 h, somatostatin 14 at doses of 180 and 210 pmol kg−1 · h−1, and somatostatin 28 at doses of 30 and 40 pmol kg−1 · h−1, induced increments of the somatostatin concentration in peripheral plasma that were similar to those recorded after ingestion of a regular meal in the same dogs. These infusions significantly inhibited the volume, bicarbonate output, and protein output of the pancreatic response to 0.25 CU kg−1 · h−1 secretin plus 20 ng kg−1 · h−1 caerulein in the same animals. These results indicate that somatostatin 28 is cleared from plasma at a slower rate than the tetradecapeptide in dogs. Hence, near-physiologic increments of plasma somatostatin concentration, when reproduced by infusing the exogenous peptides, require on a molar basis four to six times less somatostatin 28 than somatostatin 14. Under such conditions, both peptides appear capable of inhibiting the response of the exocrine pancreas to submaximal doses of secretin plus caerulein.