Determinants of bile secretion: effect of bile salt structure on bile flow and biliary cation secretion

The effect of five bile salts, deoxycholate, chenodeoxycholate, cholate, ursodeoxycholate, and ursocholate, possessing (in decreasing order) different hydrophobicity, on bile flow and biliary secretion of total calcium, magnesium, sodium, and potassium was studied in 10 patients with T-tubes. Each subject was infused intraduodenally with one or two bile salts, given separately, to produce a selective enrichment of biliary bile salts with the infused bile salt. The choleresis induced per 1-mumol increase of bile salt output was greater during the secretion of 7 beta-hydroxylated bile salts, ursodeoxycholate (0.029 ml), and ursocholate (0.027 ml), followed in decreasing order by deoxycholate (0.023 ml), chenodeoxycholate (0.019 ml), and cholate (0.009 ml). Deoxycholate stimulated the greatest increase in cation secretion per unit increase in bile salt output, followed by chenodeoxycholate and cholate. The two 7 beta-hydroxylated bile salts induced greater cation secretion than did their 7 alpha-epimers. Whereas biliary concentration of divalent cations differed depending on the structure and concentration of the infused bile salt, the concentration of monovalent cations was constant for any species and concentration of infused bile salt. Relationships between bile salt and divalent cation concentration indicate that 1 mumol of secreted biliary deoxycholate, the most hydrophobic bile salt, associates with the greatest amount of calcium (0.046 mumol) and magnesium (0.022 mumol), followed by chenodeoxycholate (0.020 and 0.010 mumol, respectively) and cholate (0.012 and 0.008 mumol, respectively). The capacity of ursodeoxycholate and ursocholate to associate with calcium and magnesium seems to be less than that of their 7 alpha-epimers. These data suggest that of the common bile salts, the more hydrophobic bile salts stimulate bile flow and cation secretion better than the more hydrophilic bile salts, whereas ursodeoxycholate and ursocholate are more effective than their more hydrophobic 7 alpha-epimers. Whereas different bile salts seem to influence the secretion of sodium and potassium mainly by virtue of their choleretic properties, the effect of bile salt structure on biliary secretion of calcium and magnesium suggests the presence of a secretory link that might be consistent with cation-bile salt binding.