1. To determine the functional significance of physiological plasma concentrations of cholecystokinin, five volunteers each received graded doses of intravenous infusions of cholecystokinin octapeptide (CCK-8). At each dose plasma concentrations of CCK-8 were determined and pancreatic and biliary outputs were measured.

2. Threshold plasma concentrations of CCK-8 for augmenting pancreatic trypsin secretion were undetectable (< 3 pmol/l), and maximal trypsin output of 21.9 ± 1.95 k-i.u./30 min was produced by 17.1 ± 6.4 pmol of CCK-8/1. Calculated half-maximal output was produced by 4.7 pmol of CCK-8/1.

3. Maximal trypsin output during infusions of CCK-8 was significantly less than that after a combination of the CCK-like peptide, caerulein, and secretin (32.95 ± 2.16 k-i.u./30 min, P < 0.001).

4. Biliary bile acid and bilirubin outputs were significantly augmented only when plasma concentrations of CCK-8 were > 5 pmol/l.

5. Plasma concentrations of CCK-8 in the low picomolar range exert significant effects on pancreatic and biliary secretion. CCK-8 fulfills the criteria for a circulating hormone.

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