Lecture 6 - OATs And OCTs (Importance In Drug Metabolism)

Question 1

What does SLC stand for?

Answer 1

Soluble Carrier transport protein

Question 2

What is SLC22?

Answer 2

Subfamily of SLCs that contain the 2 subfamilies of OATs and OCTs

Question 3

What does OATs stand for?

Answer 3

Organic Anion Transporters

Question 4

What does OCTs stand for?

Answer 4

Organic Cation Transporters

Question 5

Where are OATs usually located?

Answer 5

Localised to epithelial cells where theres a barrier between fluid compartments

Question 6

What are some examples of where OATs are expressed?

Answer 6

Kidney (between urine and plasma)
Brain (between CSF and plasma)

Question 7

What is the clinical importance of OATs?

Answer 7

Mediate uptake of antibiotics, antivirals, diuretics and NSAIDs that are organic anions

Question 8

What type of transport do substrates cross OCTs by?

Answer 8

Facilitated diffusion (use electrochemical gradient)

Question 9

Where are OCTs found?

Answer 9

MANY TISSUES

Question 10

What are some important drugs that are affected by OCT activity?

Answer 10

Cisplatin
Metformin
Amiloride

Question 11

What is the function of Amiloride?

Answer 11

Diuretic treats hypertension

Question 12

What is the function of Cisplatin?

Answer 12

Chemotherapy for cancers

Question 13

What is the function of Metformin?

Answer 13

Anti diabetic drug treats type 2 diabetes

Question 14

Do OATs and OCTs move substances into or out of cells?

Answer 14

INTO (UPTAKE TRANSPORTERS)

Question 15

If the function of OATs and/or OCTs are affected, what happens to the metabolism of drugs?

Answer 15

Affected

Question 16

If drugs are cations at physiologically pH, what transporter is important for their uptake?

Answer 16

OCTs

Question 17

Why is expression of OATs/OCTs very important for drug action?

Answer 17

Certain drugs need them to reach target site

Question 18

Why are OATs and OCTs important in drug elimination?

Answer 18

They shorten plasma half life of the drug
OATs/OCTs in kidney allow them to be removed

Question 19

What is the advantage of blocking OATs/OCTs when administering drugs?

Answer 19

Prevent their elimination by the kidney

Question 20

What is the function of probenecid ?

Answer 20

Blocks the OATs for penicillin helping increase its effectiveness

Question 21

How do OATs transport OA- from blood to kidney cell?

Answer 21

Na/K+ ATPase establishes Na= gradient
Dicarboxylate transporter tranports DC- (2º active trans) into PCT cell
OATs antiport OA- into PCT and DC- back into blood (3º active trans)

Question 22

How are OC+ removed from the blood in the kidney by OCTs?

Answer 22

OCT2 Uniporter OC+ into PCT cell
OC+ moves into filtrate via MATE and MATE2-K transporters bringing H+ into PCT

Question 23

How does metformin help treat Type 2 diabetes?

Answer 23

Reduces production of glucose by the liver

Question 24

Which transporter is important for metformin transport?

Answer 24

OCT1

Question 25

How does Cisplatin act as an anti cancer drug?

Answer 25

Enters cells of tumour Alkalinising agent Disrupts cells DNA killing cell

Question 26

What side effects are common with Cisplatin as a chemotherapy agent?

Answer 26

Kidney damage Hearing loss Sensory neuropathy

Question 27

Why does cisplatin have a high toxicity to normal cells killing cells and causing its common side effects?

Answer 27

Cisplpatin = good substrate for OCT 2 (TAKEN INTO CELL WELL) Poor substrate of MATE1 or MATE2-K (NOT REMOVED WELL) Accumulates in cell and dies