The action of the C-terminal octapeptide of cholecystokinin and related peptides on pancreatic exocrine secretion

Abstract

SUMMARY The effect of the C-terminal octapeptide of cholecystokinin-pancreozymin (CCK-PZ), caerulein, and the C-terminal tetrapeptide of gastrin on pancreatic secretion of fluid, electrolyte, amylase, and protein was studied in anaesthetized dogs prepared with pancreatic fistulae. Against background stimulation of fluid secretion with submaximal doses of secretin, all the polypeptides produced a qualitatively similar pancreatic response, causing a highly significant increase in amylase, protein, calcium, and zinc concentrations. Magnesium concentration was significantly increased only when the concentration preceding the administration of the peptide was below 100 ,u-equiv/l. Octa-CCK-PZ was 13-35 times and 20-56 times more potent than tetragastrin on weight and molar bases, respectively, as a stimulant of amylase secretion. The threshold doses were largest for amylase, lower for calcium, and lowest for zinc. A significant linear correlation was observed between amylase and calcium concentration, zinc and protein concentration, and magnesium and calcium concentration. The peptides produced some increase in secretin-induced volume flow, whereas bicarbonate, chloride, sodium, and potassium concentrations remained unchanged. The direct relation between bicarbonate concentration and flow rate was limited to rates below 1.5 ml/5 minutes. At higher rates bicarbonate and chloride concentration reached a high and low plateau, respectively, although the first five-min sample of pancreatic juice after secretin stimulation exhibited a relatively low bicarbonate and high chloride concentration compared with its voluminous flow. Chloride concentration varied inversely with bicarbonate concentration, the sum of the two anions being constant.The intestinal hormone cholecystokinin/pancreozymin (CCK-PZ), for which a partial structure has been proposed, is a single-chain polypeptide with 33 amino acid residues (Mutt and Jorpes, 1968). The C-terminal pentapeptide of CCK-PZ is structurally identical with that of the gastric hormone gastrin, and also of the decapeptide caerulein, isolated from the skin of Hyla caerulea (Anastasi, Erspamer, and Endean, 1968). Recently Plusec, Sheehan, Sabo, Williams, Kocy, and Ondetti (1970) have synthesized the C-terminal octapeptide of CCK-PZ (octa CCK-PZ) which possesses the biological activities of the full hormonal molecule.It has been demonstrated that octa CCK-PZ is more potent, on weight and molar bases, than the 'Address for correspondence: Sumio Nakajima, MD, 2nd

Calcitonin and exocrine pancreatic secretion in man: inhibition of enzymes stimulated by CCK-pancreozymin, caerulein, or calcium no response to vagal stimulation

“…Parallel excretion of calcium and magnesium was previously described in normal subjects and pancreatic insufficiency in response to secretin and CCK-PZ (Baltzer et al, 1974). The present observation that changes in magnesium output in each case resembled but did not strictly parallel changes in calcium excretion suggest that there are probably different secretory sites for both divalent cations in the human pancreas, as has been assumed also from experiments on dogs (Nakajima, 1973).…”

Effect of Caerulein on Total and Ionized Calcium Secretion in the Duodenal Juice of Man

“…Several authors observed an increase of total calcium concentration in the duodenal and pancreatic juice of man [1][2][3] and dog [4][5][6] after administration of cholccystokinin (CCK) superimposed on a continuous secre tin infusion. It has been demonstrated that pancreatic calcium was mainly bound to en zyme proteins [7][8][9][10].…”

Caerulein

“…As indicated above, caerulein appears to have a similar potency in vivo to natural porcine CCK-33 and synthetic CCK-8. Similar to CCK, it primarily stimulates enzyme secretion and synergizes with secretin on fluid secretion in dog (23,30), human (5,9,27), pigs (6), sheep (7). In the rat, similar to CCK, caerulein stimulates both a low bicarbonate fluid secretion and robust digestive enzyme secretions (12).…”