Lecture 10 - Signal transduction in Epithelia 1 (Renal)

Question 1

What are the steps of GPCR activation?

Answer 1

1) Ligand binds to receptor causing activation
2) Conformational change of G protein and exchange of GDP to GTP
3) G protein dissociates
4) Subunits and GTP interact with effectors
Effectors promote an increase in second messengers such as cAMP, Ca2+, IP3, diacylglycerol, leading to cellular response.

Question 2

What occurs in the PT?

Answer 2

ALL glucose and amino acid reabsorption (by diffusion and active transport
Most mineral salts absorption (by osmosis)

Question 3

What reabsorption occurs in DCT?

Answer 3

Some mineral salts (by active transport)

Question 4

What hormones decrease NaCl and water reabsorption?

Answer 4

atrial natriuretic peptide (ANP), guanylin, and dopamine

Question 5

What hormones increase NaCl and water reabsorption?

Answer 5

angiotensin II and aldosterone: increase NaCl and water reabsorption

Question 6

What hormone increases water reabsorption?

Answer 6

ADH/vasopressin

Question 7

What stimulates aldosterone release?

Answer 7

Angiotensin II signal transduction in adrenal cortex

Question 8

What is released in response to low BP?

Answer 8

Angiotensin II - Water-soluble ligand, uses GPCR

Question 9

What does ANGII act on?

Answer 9

ANGII binds to AT1 receptor (GPCR) on zona glomerulosa cells of adrenal cortex

Question 10

What does aldosterone act on?

Answer 10

Aldosterone lipid-soluble ligand, uses intracellular receptor to increase Na+ uptake from kidney tubules and increase blood pressure

Question 11

What is the ATI receptor?

Answer 11

ATI receptor is a GPCR that transduces a signal through Gaq and the second messengers DAG, IP3 and Ca2+

Question 12

What does IP3 signal?

Answer 12

The release of Ca+ from ER

Question 13

What does DAG activate?

Answer 13

PKC

Question 14

Angiotensin 2 binds to its receptor in the plasma membrane BECAUSE angiotensin 2 is a lipid-soluble ligand

Answer 14

C – First statement true, second false
Water-soluble ligand

Question 15

What is SGK?

Answer 15

Primary response gene for aldosterone
Decreases ENaC endocytosis and degradation, and promotes transcription of secondary response genes
e.g. epithelial sodium channel (ENaC).

Question 16

Where does aldosterone increase Na+ transport?

Answer 16

CCD

Question 17

What is ANP?

Answer 17

Atrial naturetic peptide

Question 18

What is ANP released in response to?

Answer 18

ANP released in response to HIGH blood pressure, and decreases blood volume and pressure.

Question 19

What type of receptor is the ANP receptor?

Answer 19

Guanylyl cyclase enzyme-linked receptor

Question 20

What happens when ANP is bound to its receptor?

Answer 20

Conversion of GTP to cGMP
cGMP activates PKG
PKG phosphorylated Na/K-ATPase

Question 21

What happens when Na/K-ATPase is phosphorylated?

Answer 21

Phosphorylation of Na/K-ATPase will inhibit. This stops osmotic gradient, decreasing water reabsorption and blood pressure and volume.

Question 22

What activates PKG?

Answer 22

cGMP

Question 23

Where is the ANP receptor found?

Answer 23

On basolateral membrane of collecting duct epithelial cell

Question 24

What does phosphodiesterase catalyse?

Answer 24

Phosphodiesterase catalyses cGMP to GMP

Question 25

What does ADH do?

Answer 25

ADH/vasopressin increases water reabsorption through aquaporin 2 in distal kidney

Question 26

What is ADH released in response to?

Answer 26

Increase in ECF osmolarity - dehydration

Question 27

Where is ADH released from?

Answer 27

Posterior pituitary

Question 28

What does ADH bind to?

Answer 28

ADH binds V2 (GPCR) receptor on basolateral membrane of cortical collecting duct principal cell

Question 29

What happens when V2 is activated?

Answer 29

GPCR activated, cAMP increases, PKA activated, AQP2 phosphorylated and exocytosed to apical cell surface