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Using a specific radioimmunoassay for cholecystokinin (CCK) we have studied the relation between circulating CCK concentrations and the feedback regulation of pancreatic enzyme secretion in conscious rats. Recirculation of diverted bile-pancreatic juice into the duodenum or intraduodenal perfusion of trypsin during biliary-pancreatic juice diversion produced basal output of amylase and trypsin and low portal CCK levels (<10 pmol/L). Biliary-pancreatic juice diversion or inactivation of trypsin caused increased CCK concentrations (peak values 50–100 pmol/L) and enzyme outputs. During biliary-pancreatic juice diversion, infusion of the CCK receptor antagonist proglumide suppressed the enzyme response without altering the increase in CCK. Measurement of portal and peripheral CCK during biliary-pancreatic juice diversion yielded values of 131 ± 37 and 32 ± 5 pmol/L, respectively. The peripheral CCK levels corresponded to concentrations achieved during exogenous CCK-8 infusion which resulted in similar enzyme outputs. Gel chromatography of portal plasma during diversion of biliary-pancreatic juice revealed one peak of CCK corresponding to CCK-8, and a larger peak eluted between CCK-33 and CCK-8, probably representing CCK-22. Similar CCK components were found in water extracts of jejunal mucosa, whereas the acetic acid extracts mainly contained CCK-33/39. We conclude that the negative feedback regulation of pancreatic enzyme secretion in rats is mediated by the release of CCK from the intestine and that the major molecular form of CCK in plasma is probably CCK-22.

The effect of a 550-kcal mixed meal and of an intravenous injection of pentagastrin (0.06 μg/kg body wt) upon peripheral blood serotonin concentrations has been compared in 10 carcinoid patients with hepatic metastases and healthy subjects. The fasting concentrations of blood serotonin in the patients (range 790–4500 ng/ml) were elevated compared with healthy subjects (range 71–310 ng/ml; n = 15). Urinary output of 5-hydroxyindole acetic acid was elevated in 8 patients but was in the healthy range for 2 patients. The healthy subjects (n = 9) responded to food with an increase in blood serotonin (maximum rise over mean basal of 32% ± 4%) that was significant at 60, 75, 90, and 105 min postcibal. All carcinoid patients responded to food with a comparable (25% ± 11% over basal) rise in serotonin but the pattern of release was erratic. All patients with tumor metastases exhibited symptoms of the carcinoid flush after eating, but there was no correlation between occurrence and severity of the flush and occurrence and magnitude of the rise in serotonin. Intravenous pentagastrin evoked a flush in all carcinoid patients, but there was no significant increase in peripheral blood serotonin either in the patients or in healthy subjects.