Received March 15, 2007
Revised April 10, 2007
Accepted after revision April 26, 2007
GI & Epithelial Physiology [230]
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H+-coupled nutrient, micronutrient and drug
transporters in the mammalian small intestine
David T Thwaites 1*
Catriona MH Anderson 1
1 University of Newcastle
* To whom correspondence should be addressed. E-mail: d.t.thwaites{at}ncl.ac.uk.
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Abstract |
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The H+-electrochemical gradient was
originally considered as a driving force for solute
transport only across cellular membranes of bacteria,
plants and yeast. However, in the mammalian small
intestine a H+-electrochemical gradient is
present at the epithelial brush-border membrane in the
form of an acid microclimate. Over recent years a large
number of H+-coupled cotransport mechanisms
have been identified at the luminal membrane of the
mammalian small intestine. These transporters are
responsible for the initial stage in absorption of a
remarkable variety of essential and non-essential
nutrients and micronutrients including protein digestion
products (di/tripeptides and amino acids), vitamins,
short-chain fatty acids and divalent metal ions.
H+-coupled cotransporters expressed at the
mammalian small intestinal brush-border membrane
include: the di/tripeptide transporter PepT1 (SLC15A1);
the proton-coupled amino-acid transporter PAT1
(SLC36A1); the divalent metal transporter DMT1
(SLC11A2); the organic anion transporting polypeptide
OATP2B1 (SLC02B1); the monocarboxylate transporter MCT1
(SLC16A1); the proton-coupled folate transporter PCFT (SLC46A1); the sodium-glucose linked cotransporter SGLT1 (SLC5A1); and the excitatory amino acid carrier EAAC1 (SLC1A1). Emerging research demonstrates that the optimal
intestinal absorptive capacity of certain H+-
coupled cotransporters (PepT1 and PAT1) is dependent
upon function of the brush-border
Na+/H+ exchanger NHE3 (SLC9A3).
The high oral bioavailability of a large number of
pharmaceutical compounds is due, in part, to absorptive
transport via these same H+-coupled
cotransporters. Drugs undergoing H+-coupled
cotransport across the intestinal brush-border include
those used to treat bacterial infections,
hypercholesterolaemia, hypertension, hyperglycaemia,
viral infections, allergies, epilepsy, schizophrenia,
rheumatoid arthritis and cancer.
Key Words:
Absorption, Co-transport, Epithelia
