Base secretion in rat distal colon: ionic requirements

Abstract

To evaluate the ionic requirements of colonic base secretion, segments of rat distal colon were studied under short-circuited conditions. Net base flux was composed of an active secretory component and a diffusive component. Studied in the absence of a transepithelial HCO3- concentration gradient, active base secretion was dependent on the HCO3- concentration of the bathing solution but was not influenced by the CO2 tension or pH. Base secretion appeared to saturate with a Km of 33 +/- 9 mM and was inhibited by ouabain. The diffusive component was characterized by an apparent permeability coefficient to HCO3- of 8.9 +/- 0.9 x 10(-6) cm/s. In addition to requiring HCO3- on the serosal surface, net base secretion was inhibited by reducing the Na+ concentration in the serosal medium and the Cl- concentration in the mucosal medium. These data suggest that colonic base secretion involves HCO3- entry across the basolateral surface, energized by the Na+ gradient, and HCO3- exit across the apical surface in exchange for Cl-.

Segregation of Na/H exchanger-3 and Cl/HCO3exchanger SLC26A3 (DRA) in rodent cecum and colon

“…Our finding that the rodent distal colon, like the cecum, expresses high levels of DRA but negligible NHE3 is compatible with previous reports that this segment, like the cecum, can rapidly secrete HCO 3 Ϫ in a manner that is electroneutral, coupled to Cl Ϫ absorption (7,27,28,46,66,83), and dependent on DRA function (74,79). Our results, however, are inconsistent with previous evidence that NHE3, but not NHE2, participates in electroneutral HCO 3 Ϫ -dependent NaCl absorption by the rat distal colon (5, 51); the experimental use of proximal regions of the distal colon, in which NHE3 is low but clearly present (Fig.…”

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

“…7.5 was reported for this segment. 38) This is in good agreement with previous reports that the distal colon can rapidly secrete HCO 3 Ϫ in exchange for Cl Ϫ , 26,33,88) and that this process is dependent on DRA. 46) The question thus arises which physiological role SLC26A3 Ϫ was found to be necessary for the unfolding of mucous secreted into the colonic lumen and can cross the epithelium via the pathways found in epithelial cells and outlined above.…”

“…After early in vivo studies demonstrating colonic HCO 3 Ϫ secretion, 85,86) Feldman and Stephenson developed a technique to measure HCO 3 Ϫ secretion in rat distal colon in the Ussing chamber, 87) and were able to show subsequently that in the basal state, this process is dependent on Na ϩ /K ϩ ATPase, Na ϩ in the serosal medium, and Cl Ϫ in the mucosal medium. 88) In the apical cytoplasmic membrane of the colonocyte, three mechanisms for HCO 3 Ϫ transport are operative: HCO 3 Ϫ conductance, Cl Ϫ /HCO 3 Ϫ exchange, and SCFA/HCO 3 Ϫ exchange, 26) and there is a substantial interrelationship between the three: cAMP downregulates Cl Ϫ dependent HCO 3 Ϫ secretion, while the SCFA isobutyrate inhibits both cAMP-induced and Cl Ϫ dependent HCO 3 Ϫ secretion. In order to understand these published data on a molecular basis, we recently investigated basal and agonist-stimulated HCO 3 Ϫ secretory rates in the different segments of murine colon in the presence and absence of high (150 mM) Cl Ϫ in the luminal bath (Xiao et al, unpublished) in normal mice, and those that were deficient for either of the two major anion transporters that are expressed in the apical membrane of colonic enterocytes, the anion exchanger DRA (Slc26a3) or the anion conductance CFTR, as well as for the Na ϩ /H ϩ exchanger isoform 3 (NHE3).…”

Chloride-dependent bicarbonate secretion in the mouse large intestine

“…Using the similar experimental system, Cl − -dependent HCO − 3 secretion was demonstrated in guinea pig and rat cecum (6,27) and in rat distal colon (12,13,24). Interestingly, Cl − -dependent HCO − 3 secretion was reported to be hardly observed in the proximal colon of rabbit as is the case for the mouse (23).…”