Proximal duodenal enterocyte transport: evidence for Na(+)-H+ and Cl(-)-HCO3- exchange and NaHCO3 cotransport

Abstract

The duodenum, in contrast to the jejunum, actively secretes HCO3- at a high rate, a process that protects the mucosa from acid/peptic injury. Our purpose was to define the mechanisms involved in HCO3- transport by studying the acid-base transport processes in isolated duodenal enterocytes. Individual rat duodenocytes, isolated by a combination of Ca2+ chelation and collagenase, attached to a collagen matrix were loaded with the pH-sensitive fluoroprobe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM), and intracellular pH was monitored by microfluorospectrophotometry. To identify Na(+)-H+ transport, cells in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid 1) were pulsed with NH4Cl (40 mM) in the absence and presence of amiloride and 2) were removed of Na+. To examine Cl(-)-HCO3- exchange, Cl- was removed from Ringer-HCO3- superfusate in the presence and absence of dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (H2DIDS). The NaHCO3 cotransporter was studied by addition and subtraction of Na+ to amiloride-treated and Cl(-)-depleted enterocytes perfused with Na(+)- and Cl(-)-free Ringer-HCO3- buffer with and without H2DIDS. Mammalian duodenocytes contain at least three acid-base transporters: an amiloride-sensitive Na(+)-H+ exchanger that extrudes acid, a DIDS-sensitive Cl(-)-HCO3- exchanger that extrudes base, and a NaHCO3 cotransporter, also DIDS sensitive, that functions as a base loader. These acid-base transporters likely play a key role in duodenal mucosal HCO3- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

News from the End of the Gut-How the Highly Segmental Pattern of Colonic HCO3- Transport Relates to Absorptive Function and Mucosal Integrity

“…They found that HCO 3 Ϫ secretion and Cl Ϫ absorption were both higher in the proximal than in the distal colon, which is an early documentation of segmental heterogeneity of colonic HCO 3 Ϫ secretion. 28) When Yau and Makhlouf studied HCO 3 Ϫ secretion in everted mucosal sac preparations from rat colon, they found a significantly higher secretory rate in the descending than in the ascending part, and a dependence on extraluminal Cl Ϫ , which argued for a Cl Ϫ /HCO 3 Ϫ exchange process, but also for profound species differences. 29) The characterization of the electrolyte transport proteins involved in colonic HCO 3 Ϫ transport has offered the possibility to get insight into the molecular basis for the segmental differences in colonic electrolyte transport.…”

“…The molecular nature of the pathway for HCO 3 Ϫ secretion in epithelia has been a subject of debate for decades, with focus in airway, gastroduodenal and pancreatic epithelia. [1][2][3][4][5] In all these tissues, a different composition of anion exchangers and anion conductances is expressed in the luminal membrane.…”

“…[6][7][8][9][10][11][12][13] Together with an epithelium-specific, segmentspecific and cell type specific set of basolateral acid/base transporters, [14][15][16][17] a variety of apical and basolateral membrane-bound, as well as intracellular carbonic anhydrases, 18,19) and an epithelium-specific composition of tight junction proteins that can result in anion-or cation selectivity, different "pore" sizes for ion permeation, as well as electrogenicity of the paracellular pathway, [20][21][22] these transporters enact a highly regulated scenario for HCO 3 Ϫ secretion. The HCO 3 Ϫ transport pathways of the colonic epithelium have not been studied intensely for a long time, 23) although a variety of early observations suggest that this intestinal segment may be particularly actively involved in transepithelial HCO 3 Ϫ transport. HCO 3 Ϫ output to the colonic lumen has been described already in the 1950s 24,25) and constitutes a complex process which can occur in exchange for other anions such as Cl Ϫ or short chain fatty acids (SCFAs), by passage through anion conductances, or by generation from CO 2 which perfuses to the lumen through membrane bound or mucus resident carbonic anydrases.…”

“…The HCO 3 Ϫ transport pathways of the colonic epithelium have not been studied intensely for a long time, 23) although a variety of early observations suggest that this intestinal segment may be particularly actively involved in transepithelial HCO 3 Ϫ transport. HCO 3 Ϫ output to the colonic lumen has been described already in the 1950s 24,25) and constitutes a complex process which can occur in exchange for other anions such as Cl Ϫ or short chain fatty acids (SCFAs), by passage through anion conductances, or by generation from CO 2 which perfuses to the lumen through membrane bound or mucus resident carbonic anydrases. 26) While it soon became clear that excess HCO 3 Ϫ secretion during infectious diarrhea can lead to lifethreatening metabolic acidosis, 27) the physiological functions of HCO 3 Ϫ in normal colonic epithelial physiology were less evident than in other parts of the intestinal epithelium, e.g.…”

The distribution and expression of CFTR restricts electrogenic anion secretion to the ileum of the brushtail possum, Trichosurus vulpecula

“…However, there appear to be two potential mechanisms for HCO 3 -exit across the apical membrane. The first involves the activity of a Cl-HCO 3 exchanger (Brown et al, 1989;Isenberg et al, 1993;Spiegel et al, 2003;Wang et al, 2002), most likely a member of the SLC26 family of anion exchangers (Jacob et al, 2002;Wang et al, 2002), and may be associated with spontaneous HCO 3 -secretion by the duodenum (Spiegel et al, 2003). In addition, acid or secretagogues stimulate electrogenic HCO 3 -secretion, which is independent of Cl-HCO 3 exchanger activity (Seidler et al, 1997;Spiegel et al, 2003).…”