Transport of propionate by human ileal brush-border membrane vesicles.
Human ileal brush-border membrane vesicles were employed to study the mechanisms of short-chain fatty acid (propionate) absorption especially to determine the effects of intravesicular HCO3- and the component of nonionic diffusion. Preloading the vesicles with HCO3- resulted in up to 20-fold "overshoots" of transport, and this effect was not seen with other intravesicular anions. This transport process was very fast (peak uptake 6 s) and was not due to intravesicular buffering by HCO3-. Radiolabeled propionate transport demonstrated transstimulation when the vesicles were preloaded with unlabeled propionate. An inward H+ gradient led to stimulation of propionate transport much smaller than in the presence of trans-HCO3-, whereas an inward Na+ gradient had no effect. Propionate transport was attenuated by the anion exchange inhibitors SITS and DIDS. Under HCO3- gradient conditions, propionate transport exhibited saturation kinetics with an apparent Km of 21 +/- 3 mM and a Vmax of 50 +/- 3 nmol.mg protein-1.3 s-1. Propionate transport was inhibited up to 40% by 2-5 carbon short-chain fatty acids (10 mM) but not by other organic anions. Short-chain fatty acid transport in the human ileum is Na+ independent and occurs mostly via a specific anion exchange mechanism with HCO3-. Our results also demonstrate a small component of nonionic diffusion of the protonated fatty acid (or anion exchange for OH-).
Harig
J M
JM
Gastroenterology Division, Medical College of Wisconsin, Milwaukee 53226.
Soergel
K H
KH
Barry
J A
JA
Ramaswamy
K
K
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D002264:Carboxylic Acids / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006246:Harmaline / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007477:Ions; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D011422:Propionates / Q000378:metabolism*; D014634:Valinomycin / Q000494:pharmacology
D002264:Carboxylic Acids; D002712:Chlorides; D007477:Ions; D011422:Propionates; D014634:Valinomycin; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D005665:Furosemide; D006246:Harmaline; D000086:Acetazolamide; D011339:Probenecid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid