Weanling, but not adult, rabbit colon absorbs bile acids: flux is linked to expression of putative bile acid transporters

Abstract

Intestinal handling of bile acids is age dependent; adult, but not newborn, ileum absorbs bile acids, and adult, but not weanling or newborn, distal colon secretes Cl(-) in response to bile acids. Bile acid transport involving the apical Na(+)-dependent bile acid transporter (Asbt) and lipid-binding protein (LBP) is well characterized in the ileum, but little is known about colonic bile acid transport. We investigated colonic bile acid transport and the nature of the underlying transporters and receptors. Colon from adult, weanling, and newborn rabbits was screened by semiquantitative RT-PCR for Asbt, its truncated variant t-Asbt, LBP, multidrug resistance-associated protein 3, organic solute transporter-alpha, and farnesoid X receptor. Asbt and LBP showed maximal expression in weanling and significantly less expression in adult and newborn rabbits. The ileum, but not the colon, expressed t-Asbt. Asbt, LBP, and farnesoid X receptor mRNA expression in weanling colon parallel the profile in adult ileum, a tissue designed for high bile acid absorption. To examine their functional role, transepithelial [(3)H]taurocholate transport was measured in weanling and adult colon and ileum. Under short-circuit conditions, weanling colon and ileum and adult ileum showed net bile acid absorption: 1.23 +/- 0.62, 5.53 +/- 1.20, and 11.41 +/- 3.45 nmol x cm(-2) x h(-1), respectively. However, adult colon secreted bile acids (-1.39 +/- 0.47 nmol x cm(-2) x h(-1)). We demonstrate for the first time that weanling, but not adult, distal colon shows net bile acid absorption. Thus increased expression of Asbt and LBP in weanling colon, which is associated with parallel increases in taurocholate absorption, has relevance in enterohepatic conservation of bile acids when ileal bile acid recycling is not fully developed.

Lithocholic acid attenuates cAMP-dependent Cl− secretion in human colonic epithelial T84 cells

“…Other similarities rest in the antisecretory actions of LCA (present study) and UDCA (39). Not surprisingly, the conjugated forms of these bile acids are more effective on the basolateral side, most likely due to the presence of BLM receptors and transporters (78). Furthermore, both UDCA and LCA act rapidly and appear to inhibit basolateral K ϩ conductances.…”

“…When transepithelial electrical resistance (Rt) reached values of Ն950 ⍀·cm 2 , the inserts were mounted in Ussing chambers (area: 0.33 cm 2 ; Physiologic Instruments, San Diego, CA) and bathed with oxygenated (95% O2-5% CO2) buffer (5 ml/reservoir) of the following composition (in mM): 115.4 NaCl, 5.4 KCl, 1.2 CaCl2, 1.2 MgCl2, 21.0 NaHCO3, 0.6 NaH2PO4, 2.4 Na2HPO4, pH 7.4, and 10 D-glucose, at 37°C. Transmural short-circuit current (Isc; A/cm 2 ) and Rt were monitored throughout the experiment using an automatic voltageclamp apparatus (VCC-MC6; Physiologic Instruments) as described earlier (78). Unless otherwise indicated, LCA (50 M) was added to both the apical and basolateral (bilaterally) reservoirs.…”

Lubiprostone Activates Cl− Secretion via cAMP Signaling and Increases Membrane CFTR in the Human Colon Carcinoma Cell Line, T84

“…5.4; HCO 3 -21.0; pH 7.4, and D-glucose 10, at 37°C. Transmural short-circuit currents (I sc ; lA/cm 2 ) and resistance R t were monitored throughout the experiment using the automatic voltage clamp apparatus (VCC-MC6; Physiologic Instruments, San Diego, CA) as described earlier [17]. Reagents were added to both the mucosal and serosal bathing solutions if not specified.…”

“…RT-PCR was performed according to Weihrauch et al [17]. Briefly, total RNA was isolated using TRIzol reagent (Invitrogen, Carlsbad, CA), and was treated with DNase to eliminate potential contaminating DNA (Amplification Grade DNase I, Sigma-Aldrich, St. Louis, MO).…”

Chenodeoxycholic acid stimulates Cl− secretion via cAMP signaling and increases cystic fibrosis transmembrane conductance regulator phosphorylation in T84 cells

“…Depending on the species, both a direct action of the bile acids on epithelial cells and an indirect action involving other epithelial and subepithelial elements (12,14,18,36,37) have been demonstrated. It is well recognized that in colonocytes Cl Ϫ secretion occurs by the concerted effort of apical membrane Cl Ϫ channels, chiefly the cystic fibrosis transmembrane conductance regulator (CFTR) and basolateral transporters Na ϩ -K ϩ -ATPase, Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC1), and K ϩ channels (3,28,35).…”