Organic Anion Transporting Proteins (OATPs) are influx transporters ie transport substrates from blood into organs and cells. OATPs can transport compounds that are relatively large and have a high degree of albumin binding under physiological conditions; they also mediate xenobiotic uptake.
In conjunction with the Organic Anion Transporters (OATs), the OATPs are important in hepatobiliary transport, renal secretion, intestinal absorption, and brain penetration of various compounds.
OATP
– inducers – increase OATP activity; currently none have been identified.
– inhibitors – slow or stop the rate of activity and transport.
– modulators – are compounds that interact with the OATPs to either enhance or reduce their activity.
– substrates – are compounds the OATPs transport; can also be inhibitors.
OATP Isoforms
There are 11 known isoforms of which –
- OATP1B1 + OATP1B3 have been studied extensively,
- OATP1A2 + OATP2B1 have limited data,
- the other 7 polypeptides are not well defined.
Summary of nutrition-related findings for the 11 known isoforms –
OATP1A2
Role
has either a direct or indirect role in bile salt transport.
Location
all major organs including intestines, liver, kidney, lung, bile duct, retina, placenta, prostate, testes, brain and Blood Brain Barrier.
Substrates
retinoids, T4, T3, thyroxine, epicatechin gallate.
Inhibitors
include flavonoids, Ginkgo flavonoids, apigenin, kaempferol, quercetin, fruit juice, naringin (in grapefruit and orange juice), hesperidin, grapefruit compounds (at a commonly consumed volume), apple juice, Camellia sinensis extract, epicatechin gallate, epigallocatechin gallate, catechins in green tea, pomelo juice.
OATP1B1
Included in drug discovery processes to minimise drug-drug interactions
Role
offers both monophasic (one binding site) and biphasic (two binding sites) capabilities.
Location
basolateral surface of hepatocytes (liver), kidney, intestine, blood-brain barrier, placenta, however there are many claims that this transporter is liver-specific transporter under normal physiological conditions.
Substrates
T4, T3, vitamin D3-glucuronide.
Inhibitors