AJP - Gastrointestinal and Liver Physiology, Vol 246, Issue 6 745-G749, Copyright © 1984 by American Physiological Society
Positional requirements for anionic charge for ileal absorption of bile salt analogues
L. Lack, A. Tantawi, C. Halevy and D. Rockett
Previous structure-activity studies of the ileal bile salt cotransport
system have suggested the idea that a coulombic interaction occurs between
the negative charge of the bile salt and a cationic site on the carrier.
Evidence included observations that modified bile salts with uncharged,
cationic, or zwitterionic side chains were poorly transported. They did
interact with this system as evidenced by their abilities to inhibit
transport. Another prerequisite for coulombic interaction is positional
(side-chain) specificity for the anionic grouping.
[14C]chenodeoxycholyl-N-ethanolamide-O-sulfate and the 3 alpha-sulfate
ester of chenodeoxycholyl-N-ethanolamide were tested for their in vivo
absorption from the jejunums and ileums of anesthetized guinea pigs. Active
ileal transport was estimated by subtracting jejunal absorption (passive)
from ileal absorption (active and passive). Translocation of the anionic
SO4(-) radical from the side chain to the 3 alpha position of the steroid
decreased active ileal absorption by 95%, demonstrating a positional
requirement for the anionic group for optimal transport.
