RT Journal Article
SR Electronic
T1 A New Interpretation of Salicylic Acid Transport across the Lipid Bilayer: Implications of pH-Dependent but not Carrier-Mediated Absorption from the Gastrointestinal Tract
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1175
OP 1180
VO 285
IS 3
A1 Masanori Takagi
A1 Yoko Taki
A1 Toshiyasu Sakane
A1 Tanekazu Nadai
A1 Hitoshi Sezaki
A1 Naoto Oku
A1 Shinji Yamashita
YR 1998
UL http://jpet.aspetjournals.org/content/285/3/1175.abstract
AB Transport of several monocarboxylic acids across the lipid bilayer was examined in liposomes consisting of egg yolk phosphatidylcholine and cholesterol. In the presence of inward proton gradient, salicylic acid (SA) was taken up rapidly by liposomes showing overshoot, saturation and competitive inhibition phenomena. These carrier-mediated like profiles of SA uptake can be explained by assuming a very high permeability through the liposomal membrane of protonated SA. Protonated SA in the extraliposomal solution (pH 5.8) was taken up by liposomes rapidly, followed by a redissociation to anion according to the intraliposomal pH (pH 7.5). The concentration gradient of protonated SA across the liposomal membrane is maintained until the intraliposomal pH decreased to the extraliposomal level, which facilitates the uptake of SA into liposomes. The permeability of the lipid bilayer to several compounds was estimated from the inhibitory effects of those compounds on SA uptake by liposomes. Good linear relationships were observed between their inhibitory effects on the liposomal uptake of SA and the permeability of the intestinal membrane to them determined both in vivo and in vitro. These results clearly indicate that the carrier-independent transport mechanism of monocarboxylic acids observed in liposomes significantly contributes to their absorption from the intestinal tract under physiological conditions. The American Society for Pharmacology and Experimental Therapeutics