Duodenal musosal bicarbonate secretion: secretion mechanisms, Physiological and pathophysiological importance

The present study demonstrates that the bicarbonate secreted by the duodenal mucosa originates from the duodenal epithelia. The Brunner's glands do not appear to contribute significantly to proximal duodenal mucosal bicarbonate secretion. Furthermore, bicarbonate secretion may originate from both villi and crypt cells since both cell types have the same basic set of acid-base transporters. However, functional differences between villi and crypts, secondary to different orientation of the transporters, cannot be ruled out and must await studies of polarized villi and crypt cells. The present study also demonstrates that CFTR plays a key role in bicarbonate transport across the luminal membrane either directly by transporting bicarbonate or indirectly by augmenting "recycling" of chloride needed for exchange with bicarbonate. Based on the data of this study and others, a model of the transport mechanisms involved in duodenal bicarbonate secretion in animals is proposed. By studying acid-base transporters in duodenocytes isolated from human duodenal biopsies, it is demonstrated that human duodenocytes have the same basic set of acid-base transporters as mammalian duodenocytes. This suggests that the proposed model for the bicarbonate secretion mechanisms in animals also applies for human duodenocytes. By utilizing the described novel method, it should now be possible to investigate duodenal bicarbonate secretion mechanisms at the cellular level in humans in health and disease. The present data also demonstrate that mucosal bicarbonate is of importance to both in-lumen neutralization of acid as well as neutralization of acid at the luminal surface of the mucosa, and thus to mucosal protection. In contrast to previous assumptions, the pancreas is not the only duodenal bicarbonate source of importance. Both the biliary system and the duodenal mucosa act in concert with pancreatic bicarbonate to accomplish in-lumen neutralization of acid in the duodenum. Finally, indirect evidence presented here and by others suggest that mucosal bicarbonate also plays a role in the pathogenesis of duodenal ulcer disease. However, conclusive evidence of the importance of duodenal mucosal bicarbonate secretion in ulcer pathophysiology is still lacking.