Secretagogues stimulate electrogenic HCO3- secretion in the ileum of the brushtail possum, Trichosurus vulpecula: Evidence for the role of a Na+/HCO3- cotransporter

Abstract

Fluid secretion is essential for intestinal function and, in eutherian mammals, is driven by electrogenic Cl- transport, which is dependent upon a bumetanide-sensitive, basolateral Na+/K+/2Cl - cotransporter, NKCC1. However, ileal secretion in the brushtail possum, a marsupial, involves a fundamentally different process, since NKCC1 expression is low in this tissue and the secretagogue-induced short circuit current (lsc) is insensitive to bumetanide. In view of these differences we have investigated the basis of the secretory response of the possum ileum. In the Ussing chamber the secretory lsc is independent of Cl- but dependent upon Na+ and serosal HCO 3-/CO2, suggesting that secretagogues stimulate electrogenic HCO3- secretion. In agreement with this, serosal DIDS (4,4'-diisothiocyano-stilbene-2,2'-disulfonate; 1 mmoll -1) inhibited the secretory response. However, acetazolamide (1 mmoll-1) and serosal amiloride (1 mmoll-1) had little effect, indicating that HCO3- secretion is driven by HCO3- transport from the serosal solution into the cell, rather than hydration of CO2 by carbonic anhydrase. Consistent with this the pancreatic variant of the electrogenic Na+/HCO 3- cotransporter (pNBC) is highly expressed in the ileal epithelium and is located in the basolateral membrane of the epithelial cells, predominantly in the mid region of the villi, with lower levels of expression in the crypts and no expression in the villous tips. We conclude that the secretory response of the possum ileum involves electrogenic HCO 3- secretion driven by a basolateral pNBC and that the ileal HCO3- secretion is associated with a specialised function of the possum ileum, most probably related to hindgut fermentation.