Further mechanistic study on intestinal absorption enhanced by unsaturated fatty acids: reversible effect by sulfhydryl modification.
In order to study the relationship between the sulfhydryl (SH) modification of membrane-associated proteins and the oleic acid-induced permeability enhancement of the colonic mucosa, in vitro and in situ absorption studies were performed using rat colon and carboxyfluorescein as an impermeable dye. The pretreatment of the mucosa with diamide, a bifunctional sulfhydryl modifier, in in vitro experiments with the everted colonic loops reduced the absorption enhancing effect of oleic acid in a concentration-dependent manner, less inhibitory effect, though just a little, was observed as compared to N-ethylmaleimide. The inhibition caused by the addition of diamide was absolutely restored by exposure of the mucosa to dithiothreitol. On the other hand, these SH modifiers showed no pronounced effect on the in vivo permeability of quinine which is well-known to be absorbed by a passive transport system mainly via the membrane lipid bilayer. These results obtained in the present study have identified an important role of the functional SH groups of membrane proteins on modulating the permeability alteration of the mucosal epithelium provoked by oleic acid. Furthermore, the SH proteins have been revealed as being unimportant in the intestinal absorption of lipoid-soluble compounds.
Murakami
M
M
Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
Takada
K
K
Muranishi
S
S
D000818:Animals; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D002463:Cell Membrane Permeability / Q000187:drug effects; D003106:Colon / Q000187:drug effects; D003958:Diamide / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005452:Fluoresceins / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D011803:Quinine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D005231:Fatty Acids, Unsaturated; D005452:Fluoresceins; D008565:Membrane Proteins; D009829:Oleic Acids; D013438:Sulfhydryl Compounds; D003958:Diamide; D019301:Oleic Acid; C024098:6-carboxyfluorescein; D011803:Quinine; D005033:Ethylmaleimide