Effects of monosulfate esters of taurochenodeoxycholate on bile flow and biliary lipids in hamsters.
The effect of the 3 alpha- and 7 alpha-monosulfate esters of taurochenodeoxycholate on bile flow and biliary lipids was compared to the effect of unsulfated taurochenodeoxycholate. Test bile salts were infused directly into the portal circulation through a catheter introduced into the splenic pulp. Recovery of unsulfated and sulfated bile salts was complete; no biotransformation of any of the administered compounds was noted. Equivalent choleresis was noted in response to administration of each of the test bile salts. Of particular interest, the biliary cholesterol and phospholipid content was tightly linked to biliary bile salt monosulfates; the slope of the line describing the relationship between bile salts and lipids was similar to that for the unsulfated bile salt. The critical micellar concentration of the 3 alpha- and 7 alpha-monosulfate esters was 19 mM and 18 mM, respectively. Sulfation of taurochenodeoxycholate, therefore, does not impair its bile secretory function. Despite a higher critical micellar concentration, biliary lipid excretion with monosulfate esters is equivalent to that seen with unsulfated bile salt. The role of hydrophobic/hydrophilic balance in the promotion of biliary lipid excretion may need to be redefined.
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
R D
RD
Stevens
L
L
Lack
R H
RH
Collins
W C
WC
Meyers
P G
PG
Killenberg
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives*; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D050356:Lipid Metabolism; D008297:Male; D008647:Mesocricetus; D010743:Phospholipids / Q000378:metabolism; D013329:Structure-Activity Relationship; D013655:Taurochenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D010743:Phospholipids; D002635:Chenodeoxycholic Acid; D013655:Taurochenodeoxycholic Acid; C060690:taurochenodeoxycholate-7-sulfate; C041710:taurochenodeoxycholate-3-sulfate; D002784:Cholesterol