title: Excluded volume effect of rat intestinal mucin on taurocholate/phosphatidylcholine mixed micelles.
abstract: The interaction of bile salt/phospholipid mixed micelles with an intestinal mucin has been investigated to provide the foundation for the transport of ingested fat and poorly water-soluble drugs through the intestinal mucous layer. Egg phosphatidylcholine (PC) was equilibrated with sodium taurocholate (TC) to generate several series of solutions, which had different intermicellar concentrations of TC. Within each series, each solution had the same IMC and thereby micelle sizes, but varied with respect to micelle concentration. These solutions were combined with isolated rat intestinal mucin, equilibrated, and then separated by centrifugation. The supernatant and mucin pellet were assayed for PC and TC, and the diffusion coefficient of PC was measured in the supernatant by PFG-SE NMR spectroscopy. For each series, four linear relationships were found; TC supernatant concentration plotted as a function of PC supernatant concentration; TC pellet concentration plotted as a function of PC pellet concentration; TC pellet concentration plotted as a function of TC supernatant concentration; and PC pellet concentration plotted as a function of PC supernatant concentration. Theoretical analysis of these results indicated that mucin excludes from 25 to 80% of the bile salt/phospholipid mixed micelles with greater exclusion observed with larger micelle size. There is preferential association of the taurocholate with intestinal mucin, when present in the mixed micelle region of the phase diagram. The association coupled with exclusion would allow mucin to modulate the concentration of bile salt at the epithelial surface.
authors.affiliation: Department of Pharmaceutics, University of Minnesota, 308 Harvard St. SE, Minneapolis, MN 55455, USA. wiedm001@tc.umn.edu
authors.forename: Timothy Scott
authors.initials: TS
authors.lastname: Wiedmann
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.forename: Heather
authors.initials: H
authors.lastname: Herrington
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry; D001692:Biological Transport; D002498:Centrifugation; D003956:Dialysis; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008823:Micelles; D009077:Mucins / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012492:Salts / Q000737:chemistry; D013656:Taurocholic Acid / Q000737:chemistry*
chemical_list: D001647:Bile Acids and Salts; D008823:Micelles; D009077:Mucins; D010713:Phosphatidylcholines; D010743:Phospholipids; D012492:Salts; D013656:Taurocholic Acid