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THE COLLECTING DUCT (CD) is composed of three anatomically distinct segments, cortical, outer medullary, and inner medullary collecting duct (CCD, OMCD, and IMCD, respectively), and plays an essential role in acid-base homeostasis. The CCD secretes both acid and bicarbonate by - and -cells, respectively, whereas the OMCD and IMCD are predominantly involved with acid secretion and bicarbonate reabsorption. The intercalated cells in the OMCD are exclusively of the acid-secreting -cell type. Active proton secretion across the apical membrane of the CD is largely mediated via H+-ATPase (and to some extent, H+-K+-ATPase) (25, 29). The exit across the basolateral membrane of intercalated cells in the CCD and OMCD is mediated via exchanger. The OMCD has the highest rate of H+ secretion, and therefore absorption, of the CD segments (25). As a result, the OMCD has been regarded as a major regulator of acid-base homeostasis.
The apical H+-ATPase in intercalated cells of the OMCD belongs to the family of V-type ATPase and is inhibited by bafilomycin (2, 5, 7, 8, 25, 26). The apical H+-K+-ATPase in the OMCD is likely a variant of gastric H-K-ATPase (29). This conclusion is based on the studies that demonstrated the inhibition of net bicarbonate reabsorption by Schering 28080 in OMCD (4, 29, 38). The exchanger anion exchanger-1 (AE1), a variant of red cell band 3, has been localized on the basolateral membrane of intercalated cells in the OMCD (18, 25, 32-35). However, the possibility that other basolateral exchanger(s) may contribute to net bicarbonate reabsorption in this nephron segment exists.

Recent molecular studies identified a large, highly conserved family of membrane proteins (designated as SLC26A) many of which have been shown to transport anions. Three closely related members of this family are downregulated in adenoma (DRA or SLC26A3), Pendrin (PDS or SLC26A4), and PAT1 (CFEX or SLC26A6) (11, 12, 15, 16, 28). All three transporters mediate exchange (13, 19, 27, 30, 37, 39). DRA is expressed on the apical membranes of colonocytes, whereas PAT1 or CFEX is expressed on the apical membranes of kidney proximal tubule and duodenum (12, 15, 19, 37). Pendrin mRNA expression is detected in proximal tubule and CCD (30, 36). However, immunocytochemical studies localize pendrin only to the apical membrane of a subpopulation of CCD cells distinct from -intercalated cells, which are thought to be -intercalated cells and non--, non--intercalated cells (14, 22, 23, 30, 36).