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Physiological significance of secretin in the pancreatic bicarbonate secretion. II. Pancreatic bicarbonate response to a physiological increase in plasma secretin concentration.

The pancreatic response to physiological concentrations of secretin obtained after minute boluses of exogenous secretin was studied in 16 normal volunteers. Output of bicarbonate into the duodenum was measured by duodenal aspiration in 5 subjects and by endoscopic cannulation of the pancreatic duct in 11 subjects. Pure natural porcine secretin was injected intravenously in doses of 125, 250, and 500 fmol x kg-1 body weight (0.0013, 0.0027, and 0.0054 clinical units x kg-1). All three doses of secretin increased plasma secretin concentration, duodenal bicarbonate concentration, and duodenal bicarbonate output significantly. The bicarbonate output measured by the two techniques did not differ significantly. The increments in median plasma secretin concentration were 1.6, 3.0, and 6.4 pmol x 1(-1) after secretin, 125, 250 and 500 fmol x kg-1, and the corresponding 15-min bicarbonate output 283, 442, and 1435 micromol, respectively. The concentrations of secretin in plasma found after these doses of secretin are of the same order of magnitude as the secretin concentrations found during physiological conditions in man. It is concluded that the physiological concentrations or secretin influence pancreatic bicarbonate secretion.

Bicarbonates

Comparison of the biological potency of a new synthetic preparation of secretin with that of natural porcine secretin in the dog.

The biological activity of the new synthetic secretin, Roche, on exocrine pancreatic secretion was determined in conscious dogs with chronic gastric and duodenal fistulae and compared with that of pure porcine secretin (GIH, Karolinska Institutet, Stockholm). The two secretin preparations were found to be equipotent as to pancreatic volume and bicarbonate response on a molar basis. It was concluded that the new synthetic secretin is useful for clinical and research purposes.

Animals

Effect of low dose secretin and caerulein on pure pancreatic bicarbonate secretion and plasma secretin in man.

In six healthy volunteers pure pancreatic juice was obtained by endoscopic cannulation of the main pancreatic duct. Following a 20-min basal period, secretin (0.03 CU/kg, h) was intravenously infused alone for 20 min and then with caerulein 15 ng/kg, h for further 20 min. From a basal level of 28 +/- 13 mu mol/5 min, secretin by itself significantly increased pancreatic bicarbonate to 182 +/- 24 mu mol/5 min. A further significant two-fold increase to 396 +/- 50 mu mol/5 min was observed during caerulein. The increment in plasma secretin of 2.1 +/- 0.3 pmol/l is comparable to the rise that may be observed post-prandially. It is concluded that secretin in combination with cholecystokinin may indeed play a physiological role in the regulation of duodenal pH.

Adult

Physiological significance of secretin in the pancreatic bicarbonate secretion. I. Responsiveness of the secretin-releasing system in the upper duodenum.

In nine normal subjects intraduodenal pH was measured by means of a glass electrode placed in the passage from the first to the second part of the duodenum. The physiological variations in pH were simulated by intraduodenal injection of 2.5, 5, or 10 ml of 0.1 mol x 1(-1) HCl and subsequent neutralization by injection of bicarbonate. A total of 26 injections of acid was followed by a pH spike from a median pH of 7.0 to a median of pH 2.1 Median spike duration was 45 sec. The concentration of secretin in plasma increased from a median of 1.2 pmol x 1(-1) to a peak value of 2.2 pmol x 1(-1) after 4 min. It is concluded that the secretin response to a brief acidification of the first 4--6 cm of the duodenum is sufficient to explain the physiological variations in the concentration of secretin in human plasma.

Bicarbonates

Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig. Structural requirements for effects of vasoactive intestinal peptide and secretin on cellular adenosine 3':5'-monophosphate.

Secretin and vasoactive intestinal peptide (VIP), but not glucagon, stimulate accumulation of cyclic AMP in dispersed guinea pig pancreatic acinar cells. Secretin stimulated cellular accumulation of cyclic AMP by interacting with a single class of high affinity receptors. On the other hand, the dose-response curve for VIP-stimulated cellular cyclic AMP was biphasic and reflected interaction of this peptide with two classes of receptors. Results obtained with synthetic fragments of VIP and secretin indicate that the receptor having a high affinity for VIP has a low affinity for secretin, interacts with, but does not distinguish among, secretin, secretin 5-27 and [6-tyrosine] secretin or among secretin 14-27, VIP 14-28, VIP 15-28, and increases cellular cyclic AMP when occupied by VIP, but not when occupied by secretin, [6-tyrosine] secretin, or secretin 1-14. The receptor having a low affinity for VIP has a high affinity for secretin, interacts with and distinguishes among secretin, secretin 5-27, and [6-tyrosine] secretin, interacts with secretin 14-27 but not with VIP 14-28 or VIP 15-28, and increases cellular cyclic AMP when occupied by VIP, secretin, [6-tyrosine] secretin, or secretin 1-14.

Animals

Effect of glucagon on secretin-stimulated bile flow.

The effect of glucagon on secretin-stimulated bile flow was evaluated in dogs with chronic biliary and gastric fistulas. Evaluation of the effects of secretin and glucagon alone on hepatic bile flow indicated that the calculated maximal response (CMR) values of the two agents were similar. Secretin increased the bicarbonate concentration in hepatic bile whereas glucagon did not, suggesting basic differences in mechanism of action. Administration of glucagon to secretin-stimulated bile flow produced an increase in bile flow while decreasing the bicarbonate concentration in secretin-stimulated bile. Since the maximal response for bile flow to glucagon and secretin was significantly greater than the maximal response to either agent alone, glucagon produced potentiation of secretin-stimulated bile. Glucagon increased the CMR value of secretin-stimulated bile from 513 mul/min for secretin alone to 692 mul/min for secretin and glucagon. This was associated with no significant change in the values of the respective D50S. These data suggest that glucagon produced a noncompetitive augmentation of secretin-stimulated bile flow and suggest that the two agents do not utilize the same receptor to stimulate bile flow.

Animals