Pancreatic response to intestinal perfusion with lactic acid or acidified albumin

To test the hypothesis that the permeability of weak acids across the intestinal mucosa affects their ability to stimulate pancreatic bicarbonate output, we compared pancreatic bicarbonate secretion in response to intestinal perfusion with an acid presumed to be permeable to cell membranes, lactic acid (90 daltons), and an acid presumed to be impermeable, acidified bovine serum albumin (about 70,000 daltons). These two substances have similar titration curves from pH 2.00 to pH 4.50. In four conscious dogs with pancreatic fistulas, solutions of these weak acids were perfused at 50 ml/15 min into the intestine at concentrations adjusted to deliver 1, 2, or 4 mmol/15 min of acid titratable to pH 4.50 (threshold pH for bicarbonate stimulation) from an initial pH of 2.00 or 3.50. At both pH 2.00 and 3.50 and at all titratable acid loads, bicarbonate secretory responses to lactic acid and acidified albumin were not significantly different. Equal titratable acid loads of HCl produced much larger secretory responses. The data do not support the hypothesis that permeability of weak acids is a factor, but confirm the observation that weak acids are less potent than strong acids in stimulating pancreatic bicarbonate secretion.