Pancreatic Bicarbonate Secretion Involves Two Proton Pumps

Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H+/HCO3- transporters, which depend on gradients created by the Na+/K+ -ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H+ -K+ -ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H+ -K+ pump inhibitors and ion substitutions. Gastric and non-gastric H+ -K+ pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H+/HCO3- and fluid transport shows that the H+ -K+ pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H+ -K+ pumps in pathophysiology.