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1. The isolated rat pancreas was perfused with physiological salt solutions of varying composition. Flow of pancreatic juice and output of amylase during rest and after stimulation with pure secretin, pure cholecystokinin-pancreozymin (CCK-PZ), caerulein or acetylcholine (ACh) were measured. 2. Basal fluid secretion was abolished replacing perfusion fluid NA+ or Cl- by Tris+ or SO42- respectively. Readmission of Na+ or Cl- caused a transient increase above the normal control level of both fluid and amylase output. Exposure to K+-free solution severely reduced fluid output and K+ readmission resulted in a transient increase in secretory rate. 3. Maximal stimulation with ACh (10(-7) M), CCK-PZ (1-5 X 10(-10) M) or caerulein (10(-10) M) caused marked sustained fluid and amylase secretion. Maximal secretin stimulation (5-7 X 10(-9) M) caused marked sustained fluid but only a small sustained amylase secretion following an initial transient. 4. Under continuous secretin stimulation, replacement of the CO2/HCO3-buffered control fluid by a CO2/HCO3-free Tris buffered solution caused a sharp decrease in pancreatic juice flow. In the absence of extracellular CO2/HCO3-secretin did not evoke fluid or enzyme secretion. In contrast the effects of ACh, CCK-PZ or caerulein were independent on CO2/HCO3-. Monobutyryl cyclic AMP (10(-3) M) caused marked sustained fluid secretion and transient enzyme secretion. The effect was entirely dependent on the presence of CO2/HCO3-in the perfusion fluid. 5. Ouabain (10(-4)-10(-3) M) markedly inhibited both secretin- and caerulein-evoked fluid secretion while caerulein-evoked amylase secretion was hardly affected. Similar findings were made with K+-free solution. 6. The effect of maximal secretin stimulation on amylase secretion was greatly augmented in the presence of a maximally stimulating concentration of caerulein. The effects on fluid secretion of secretin and caerulein were simply additive. The effects of secretin on both amylase and fluid secretion, in the presence of caerulein, were entirely dependent on the presence of CO2/HCO3- in the perfusion fluid. 7. We conclude that two different fluid secretion processes occur in the rat exocrine pancreas. One stimulated by ACh and CCK-PZ, that is independent of extracellular CO2/HCO3- and another stimulated by secretin involving H+ or HCO3-transport. Only the effects of secretin seem to be mediated by intracellular cyclic AMP.

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