Ion Transport In Renal Physiology:

Question 1

What are OATs?

Answer 1

• Organic ion transporters.
• Selective for a wide range of negatively charged molecules (multi/poly specific).
• Have a central role in dealing with drug metabolites (renal excretion).
• Expressed in many tissues.
• 11 OAT family members.

Question 2

Describe the transport of organic anions in the renal tubules:

Answer 2

• Primary energy source for OAT’s comes from the Na+/k+ ATPase pump.
• Na+ gradient drives secondary active transport of the dicarboxylate anion from the plasma.
• Once inside the cell the dicarboxylate organic anion can be used to counter transport the organic anion.
• The dicarboxylate is the transported back into the plasma via tertairy active transport.
• Organic anions are transported into the lumen by facilitated diffusion ( using multi drug resistant proteins).

Question 3

Name some common drugs that OAT mediate the uptake of:

Answer 3

• Negatively charged drugs (anions).

- Antibiotics, antivirals, diuretics, NSAIDs.

Question 4

What are OCTs?

Answer 4

• Poly specific catonic ( positively charged) substrate transporers.
• Six OTC family members.
• Expressed in many tissues.

Question 5

Describe the transport of cations (+ve charge) in the renal tubles:

Answer 5

• Uses large favorable electrochemical gradient of -70mv to directly dirve OC transport into the proximal tubule epithelial cell.
• Multidrug and toxin extruson proteins (MATE) 1-2 transport OCs across the apical membrane.
• Final step is uses the H+ gradient to transport to OCs into the urine. The negative membrane potential means that the H+/OC+ exchange is strongly favoured. (Tertiary active transport via MATE transporters).

Question 6

Name some common drugs effected by OCT activity:

Answer 6

• Atenolol (Beta blocker)
• Metformin ( Used to treat type 2 diabetes)
• Amiloride (Diuretic used to treat hypertension)

Question 7

What problems can arise with metformin and the OCT1?

Answer 7

• Metformin ususally decreases hepatic glucose production.
• Some patients can express a polymorphism (multiple forms) for OTC1 resulting in OTC1 with reduced activity.
• Therefore the helatic uptake of metformin is reduced, reducing its antidiabetic effects.
• Circulating glucose levels are therefore raised above those espected.

Question 8

How does amiloride work?

Answer 8

• Antihypertensive drug - diurectic.
• It inhibits Na+ reuptake into the proximal tubule of the kidney, and Na+ is excreted instead.
• Water is therefore also excreted, reducing blood volume and therefore blood pressure.