Organic anion and cation transporters

Question 1

Organic anion transporters (OAT)

Answer 1

polyspecific
transported anionic substrates (negative charge)
kidney, liver, brain etc

Question 2

Substrates for OAT

Answer 2

negatively charged common drugs (antibiotics, NSAID’s, antivirals, nutrients, diuretics)

Natural substances (butyrate, carnitine, sex steroids)

Question 3

Summary of OA transport into proximal tubule

Answer 3

OA is in capillary (eg drug taken)

Na+K+ATPase pumps sodium out of proximal tubule
(high Na in capillary now)

Na+ goes into proximal tubule through DCT (down conc gradient) with Dicarboxylate

Dicarboxylate accumulates in proximal tubule

Leaves proximal tubule (down conc gradient) back to capillary via OAT
OA moves in via OAT as this happens

Question 4

What happens after OA is in proximal tubule?

Answer 4

goes into filtrate via multidrug resistance protein (MRP) or ABC cassette protein

Question 5

How do OATs influence cell signalling?

Answer 5

regulate levels of metabolites and signalling molecules
contribute to homestasis
interorgan communication
Interorganismal communication (eg molecules across placenta/breast milk)

Question 6

What are OCT transporters?

Answer 6

Organic cation transporters
polyspecific
transport positive substrate

Question 7

examples of OCT and where expressed

Answer 7

OCT 1-3
MATE 1-2
PMAT

adipose tissue, brain, heart, glands, kidney

Question 8

Types of transport in OA filtration

Answer 8

Primary active - Na+K+ATPase
Secondary Active - DCT
Tertiary active OAT

Question 9

OC transport into proximal tubule

Answer 9

OC positively charged
driven by electrochemical gradient (-ve inside cell)
move into proximal tubule via OCT2

Question 10

How do OC pass into filtrate?

Answer 10

Via MATE transporters

Driven by pH gradient (acidic urine so H moves into proximal and OC moves into filtrate)

Question 11

Effect of OAT and OCT on drugs?

Answer 11

Drugs could be excreted into urine

Affect dosage

Question 12

What is metformin?

Answer 12

Anti diabetic drug

Decreases hepatic glucose production

Question 13

How can OCT affect drug availability? Diabetes example

Answer 13

Polymorphism OCT1
OCT1 - decreased ability
Hepatic uptake of Metformin can be reduced
Reduces effects

Question 14

How can OCT transporters cause toxic accumulation of drugs?

Answer 14

Good substrate for OCT2
Bad substrate for MATE1 or MATE2/2K
Toxic build up in proximal tubule

Question 15

example of toxic OCT

Answer 15

Cisplatin
Great OCT2 substrate (good for cancer cells)
Poor substrate for MATE1 and MATE2/2K
reduced renal excretion
toxic build up in proximal tubule cell
Nephrotoxicity