Lecture 10

Question 1

Briefly describe the cellular signalling/signal transduction pathways in epithelia

Answer 1

There is a stimulus which causes a ligand to be released. This binds to the receptor in the membrane or intracellularly. There is signal transduction through a 2nd messenger or other wats. We then need to be able to turn it off and so there is negative feedback

Question 2

Where are receptors location and what sorts of things bind to them?

Answer 2

Water soluble ligands bind to plasma membrane receptors and lipid-soluble ligands bind to cytoplasmic or nuclear receptor

Question 3

What is an example of a lipid soluble ligand that binds to a receptor inside the cell?

Answer 3

a steroid

Question 4

Lipid soluble ligands tend to alter what?

Answer 4

they alter gene expression

Question 5

Which is faster at causing an effect, water-soluble or lipid-soluble ligands. Why is this?

Answer 5

The water soluble ones because lipid soluble ligands alter gene expression and so there needs to be time for the genes to transcribe, translate and for there to movement of the required genes

Question 6

Briefly describe G-protein coupled receptors

Answer 6

There is a receptor and a G-protein which is made up of an α, β, and γ subunit. When the ligand binds to the receptor, the G-protein becomes associated with the receptor. GTP is converted to GDP and then there is dissociation of these subunits and they can go off and do stuff

Question 7

What is the function of the kidney?

Answer 7

it filters blood removing wastes and extra water to make urine

Question 8

What does the kidney control?

Answer 8

blood pressure

Question 9

What are the three main hormones that regulate NaCl and water transport pathways in the kidney tubules?

Answer 9

• angiotensin II and aldosterone
• atrial natriuretic peptide (ANP)
• antidiuretic hormone/vasopressin

Question 10

What is the purpose of angiotensin II and aldosterone?

Answer 10

to increase the NaCl and water reabsorption to increase blood pressure

Question 11

What is the purpose of atrial natriuretic peptide?

Answer 11

to decrease NaCl and water reabsorption

Question 12

What is the purpose of antidiuretic hormone/vasopressin?

Answer 12

to mainly increase water reabsorption

Question 13

Briefly describe the angiotensin II signal transduction in the adrenal cortex stimulating aldosterone release

Answer 13

In response to a low blood pressure, angiotensin || acts on the adrenal glands which release aldosterone which causes an increase in the Na+ uptake from the kidney tubules and increase blood pressure

Question 14

What stimulates angiotensin II signal transduction in the adrenal cortex?

Answer 14

low blood pressure

Question 15

Describe the angiotensin II signal transduction in the adrenal cortex

Answer 15

In response to low blood pressure (sensed via low perfusion pressure in the kidneys and a decrease in NaCl to the macula densa) renin is released from the kidneys and this cleaves angiotensinogen (from the liver) to form angiotensin I which is further cleaved by ACE to form angiotensin II. Angiotensin II binds to the AT1 receptor on the zona glomerulosa cells of the adrenal cortex

Question 16

How does the kidney know that there is low blood pressure?

Answer 16

there is low perfusion pressure in the kidneys and a decrease in NaCl to the macula densa

Question 17

What is released from the adrenal cortex when angiotensin II binds?

Answer 17

aldosterone

Question 18

Explain how the binding of angiotensin II to the AT1 receptor of the zona glomerulosa in the adrenal cortex occurs

Answer 18

The AT1 receptor is a GPCR with a G-protein complex associated with it. When angiotensin II binds to this receptor, there is release of aldosterone which has effects on the cortical collecting duct of the kidney to cause Increase Na+ uptake from kidney tubules and increase blood pressure

Question 19

Where does aldosterone have effects?

Answer 19

on the cortical collecting ducts of the kidney

Question 20

Describe the angiotensin II signal transduction in the adrenal cortex

Answer 20

In response to low blood pressure (detected as low perfusion pressure in the kidneys and a decrease in NaCl to macula densa), renin is released from the kidneys which cleaves angiotensinogen to angiotensinogen I. This is further cleaved by ACE to angiotensinogen II. This binds to the AT1 receptor on the zona glomerulosa cells of the adrenal cortex

Question 21

Where is angiotensinogen released from?

Answer 21

The liver

Question 22

Describe what happens when angiotensin II binds to the AT1 receptor in the zona glomerulosa cells

Answer 22

The AT1 receptor is an GPCR so when angiotensin II binds to the receptor, the g protein dissociates and the α subunit interacts with phospholipase C. This breaks down PIP2 to IP3 and DAG which increase aldosterone levels. DAG activates PKC which helps with the synthesis of aldosterone. IP3 binds to IP3R3 in the ER and this releases Ca2+ from the ER and this drives aldosterone synthesis and release from the adrenal cortex

Question 23

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

Answer 23

true, false

Question 24

Is aldosterone a lipid soluble molecule? Why or why not?

Answer 24

Yes because it is a steroid hormone

Question 25

Describe how lipid soluble molecules get into the cells and what they do once in there

Answer 25

Because it is lipid soluble, it diffuses into the cell. It binds to its intracellular receptor to form a receptor complex. This goes into the nucleus to activate primary response genes which act to do two things.

Question 26

What are the two different things that primary response genes do when they are activated by the aldosterone-receptor complex?

Answer 26

1. turn on secondary response genes | 2. shut off further expression of primary response genes in negative feedback

Question 27

Describe how aldosterone molecules get into the cells and what it does once it is in there

Answer 27

Because it is lipid soluble, aldosterone diffuses into the cell. It binds to its intracellular receptor called MR to form a receptor complex. This goes into the nucleus to activate the transcription of SGK genes

Question 28

What is the purpose of the SGK gene? | 2

Answer 28

1. It decrease the ENaC (epithelial Na+ channel in the apical membrane) endocytosis ie. stops it being retrieved from the membrane, and degradation which means that ENaC that is already at the membrane will stay there. This means Na+ can come down its concentration gradient from the apical membrane (urine) into the cell 2. it also promotes transcription of secondary response genes (ENaC)

Question 29

What is the overall effect of the SGK gene?

Answer 29

Both of the purposes lead to an increase in the Na+ transport, increased Na+ in the ECF, water retention and thus an increase in blood volume and blood pressure

Question 30

How can we switch off the angiotensin II signal transduction when the blood pressure is back to normal?

Answer 30

When BP is back to normal, there is no renin released and so angiotensinogen remains so there is less angiotensin I and hence angiotensin II levels decrease. Even if there was angiotensin II around, the receptors are endocytosed so there is no receptor for it to bind to. There is an activation of GTPase in glomerulosa cells so if any GTP is made, it gets converted back to GDP. If this doesn't work, we get increased expression of Ca2+ pump of the ER so Ca2+ goes back into the ER so there is no aldosterone expression

Question 31

If blood pressure gets too high, ________ can be released

Answer 31

ANP

Question 32

The ANP receptor is what kind of receptor?

Answer 32

an enzyme linked receptor

Question 33

What happens when ANP binds to its enzyme-linked receptor?

Answer 33

The receptor contains guanylyl cyclase which catalyses GTP to cGMP and the increase in cGMP activates PKG. PKG phosphorylates Na+/K+ ATPase on the basolateral side to decrease its activity which means that Na+ is not pumped out of the cell. This means that there is no osmotic gradient so no H2O comes in so there is a decrease in blood pressure and blood volume

Question 34

Where is ANP released from? What is this in response to?

Answer 34

If there is an increase in blood pressure, the atria stretch more which causes ANP to be released from cells in the heart which then bind to receptors

Question 35

How can we stop the release of ANP?

Answer 35

Phosphodiesterase converts cGMP to GMP which means that cGMP can't activate PKG. If there is less stretch, there is less ANP being released ad so there is endocytosis of the ANP receptor so it can't bind to ANP to start the signal transduction pathway

Question 36

What is released when we are dehydrated?

Answer 36

ADH/vasopressin

Question 37

Describe what happens when ADH binds to its receptor

Answer 37

ADH binds to its V2 receptor (a GPCR). This activates a G-protein and this activates adenylyl cyclase. This catalyses the conversion of ATP to cyclic AMP so the levels of cAMP increase. This increase in cAMP activates PKA which phosphorylates an aquaporin 2 channel which normally sit in vesicles in the cell but once phosphorylated, they move to the membrane. This increase the H2O absorption from the urine and then it gets into the blood through aquaporin 3 or 4

Question 38

Where is ADH released from?

Answer 38

the posterior pituitary gland

Question 39

When is ADH released?

Answer 39

In response to ECF osmolarity increase

Question 40

How can we turn off the ADH signalling pathway when we drink too much water?

Answer 40

There is no ADH/AVP released from the posterior pituitary gland when the ECF osmolarity is back to normal. The V2 receptor is endocytosed so there is no cAMP increase, PKA is inactive, AQP2 is not phosphorylated and there is less water reabsorption