Absence of a relationship between arterial pH and pancreatic bicarbonate secretion in the isolated perfused cat pancreas.

1. The secretion rate of bicarbonate by the isolated saline-perfused cat pancreas was linearly related to the bicarbonate concentration of the arterial inflow at constant PCO2 and at high volume rates of secretion. 2. Pancreatic bicarbonate secretion was independent of arterial inflow pH at constant bicarbonate concentrations when the pH was manipulated by alterations in the PCO2 at high volume rates of secretion. 3. A small but statistically significant linear relationship existed between the pH of the arterial inflow and bicarbonate secretion at constant PCO2 after inhibition of carbonic anhydrase by acetazolamide. Under the same conditions no relationship was found between bicarbonate secretion and arterial inflow pH when the perfusate bicarbonate concentration was kept constant and the PCO2 varied. 4. When the volume rate of secretion was reduced by about 60-70% of maximum no relationship was found to exist between arterial inflow pH and bicarbonate secretion at constant bicarbonate concentration in the perfusate. There was also no relationship between inflow pH and bicarbonate secretion at constant PCO2 down to a pH of 7.3 until the bicarbonate concentration of the perfusate was reduced below 10 mM, when the secretion rate fell off rapidly. 5. A linear relationship was found to exist between the volume rate of secretion and the PCO2 of the pancreatic juice and the output of lactate both in the isolated saline-perfused gland and the blood-perfused pancreas in situ. 6. At high rates of secretion the PCO2 of the pancreatic juice was always higher than that of either the arterial inflow or the venous outflow. There is therefore no gradient for the passive movement of carbon dioxide between the arterial inflow and the pancreatic juice. 7. Inhibition of secretion with acetazolamide caused a fall in the PCO2 of pancreatic juice and increased the output of lactate. The secretion of lactate was not due to hypoxia as it also occurred in the blood-perfused gland in situ which had normal haemoglobin concentrations and oxygen saturation. 8. It is concluded that the secretion of bicarbonate is independent of arterial pH but critically dependent upon the arterial concentration of the bicarbonate ion. These experiments do not support the concept that the secretion of protons over the basolateral membrane is the major primary event in pancreatic secretion of bicarbonate.