Sodium taurocholate transporting

The structure of cholic acid helps us understand how bile salts such as sodium taurocholate promote the transport of lipids through a water-rich environment. The bottom face of the molecule bear s all of the polar groups, and the top face is exclusively hydrocarbon-like. Bile salts emulsify fats by forming micelles in which the fats are on the inside and the bile salts are on the outside. The hydrophobic face of the bile salt associates with the fat that is inside the micelle the hydrophilic face is in contact with water on the outside. 

Figure 2.1 Hepatocyte basolateral bile acid transporters. Protein-bound bile acids returning in portal blood are taken up by the hepatocyte via the sodium taurocholate co-transporting polypeptide (NTCP) and organic-anion-transporting polypeptide (OATP). In cholestasis bile acids may be returned to blood by the multi-drug-resistance-associated protein 3 (MRP3).

Both specificity studies confirmed that bromosulphthalein (BSP) competitively inhibited taurocholate transport by NTCP and OATP. This is in conflict with reports that BSP transport was not sodium dependent, suggesting that OATP was responsible.The reason for this dilference is not clear but may reflect dilferences in the approaches, using isolated rat hepatocytes or transfection to produce cells that stably express the protein. Choice of cell line may also be important as expression of MEH also showed dilferences, with no demonstrable Na" -dependent transport of taurocholate in Syrian hamster kidney cells or oocytes but Na" -dependent transport was shown in Mardin-Darby canine... 

Kim RB, Leake B, Cvetkovic M, Roden MM, Nadeau J, Walubo A, Wilkinson GR (1999) Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther 291, 1204-1209. 

Kouzuki, H., Suzuki, H., Ito, K., Ohashi, R. and Sugiyama, Y. (1998) Contribution of sodium taurocholate co-transporting polypeptide to the uptake of its possible substrates into rat hepatocytes. The Journal of Pharmacology and Experimental Therapeutics, 286, 1043-1050. 

Fig. 5. Transport of bile acids in the enterohepatic circulation. The left and right sides of the figure depict a liver and intestinal cell, respectively. Bile acids (BA) are made from unesterified cholesterol (UC) in the liver. The movement of bile acids in the enterohepatic circulation is vectorial. The major transporters thought to be responsible for the entry and exit of bile acids in liver and intestinal cells are sodium/taurocholate cotransporting polypeptide (ntcp SLClOAl), bile salt export pump (bsep ABCBll), apical/sodium bile acid cotransporter (asbt SLC10A2), and organic solute transporters a/p, (Osta/P).

Surpuriya, V., and Higuchi, W.I. (1974) Enhancing Effect of Calcium Ions on Transport of Cholesterol from Aqueous Sodium Taurocholate-Lecithin Micellar Phase to Oil Phase, J. Pharm. Sci. 63,1325 1327. 

Ouabain inhibits sodium extrusion from the cell and thereby obliterates its critical concentration differences. Ouabain acts on the energy utilization step for the active extrusion of sodium ions, as evidenced by its inhibition of transport adenosine triphosphatase (20). The inhibition of bile salt transport by ouabain (21,22) resembles similar actions against other transport systems (e.g., those for amino acids and sugars). The omission of cations other than sodium from the incubation media does not greatly impair taurocholate transport (22). 

ABC, ATP-binding cassette transporter superfamily ASBT, apical sodium-dependent bile salt transporter BCRP, breast cancer resistance protein BSEP, bile salt export pump MDRl, multidrug resistance MRR multidrug resistance-related protein NTCP, sodium taurocholate cotransporting polypeptide OAT, organic anion transporter OCT, organic cation transporter SLC, solute-linked carrier transporter family SLCO, solute-linked carrier organic anion transporter family. 

Agents capable of promoting absorption and/or permeation were discussed in a recent review . The intestinal absorption of sulfamethoxypyridazine, diphenhydramine, salicylic acid, p-hydroxybenzoic acid and heparin was facilitated in the presence of surfactants, as was the intramuscular absorption of enduracidin . The effect of sodium taurodeoxycholate on drug transport across biological barriers was studied " . Mixed micellar solutions of a fatty acid, a monoglyceride and sodium taurocholate had a greater effect on the absorption of... 

Wilkinson,. Pharmacol. Exp. Ther., 291, 1204 (1999). Modulation by Drugs of Human Hepatic Sodium-Dependent Bile Acid Transporter (Sodium Taurocholate Cotransporting Polypeptide) Activity. 

A review by Heaton and Morris [221] recalls the development of ideas about bile salts and "bitter humour. The enterohepatic circulation of the bile salts was an early discovery the site of absorption of the bile salts in the intestine was a later topic of study. Absorption by the jejunum of sodium taurocholate is negligible both below and above the CMC and it was absorbed mostly in the ileum [222]. It has been established that bile salts are absorbed by an active transport process, absorption being related to the number of hydroxyl groups on the molecule. 

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