Session 2 (Intracellular Signaling Pathways)

Question 1

How many transmembrane regions do GPCRs have?

Answer 1

7 (they are said to be 7TM proteins)

Question 2

How do antagonists work?

Answer 2

Binds to a receptor but DOES NOT activate

Question 3

Where are the N and C terminals of GPCRs?

Answer 3

N- extracellular

C- intracellular

Question 4

What is a G protein structure?

Answer 4

An alpha subunit (with a GDP) bound to a beta-gamma subunit

Question 5

What happens when a G protein is activated?

Answer 5

GDP is released, replaced by GTP (alpha subunit has high affinity for readily available GTP) and subsequently the alpha subunit loses affinity for the beta-gamma subunit

Question 6

How is a G protein terminated/deactivated?

Answer 6

GTPase hydrolyses (slowly) reaction of GTP->GDP+Pi which means alpha regains high affinity for beta-gamma subunits

Question 7

Where do the GPCR processes occur and why?

Answer 7

On the plasma membrane

So all key components are concentrated, which speeds up signalling pathway thus cellular responses are faster

Question 8

What effector does the Gi protein activate?

Answer 8

Adenylyl cyclase

Question 9

What effector does the Gs protein activate?

Answer 9

Adenylyl cyclase

Question 10

What effector does the Gq protein activate?

Answer 10

Phospholipase C

Question 11

What type of response does a Gi protein produce?

Answer 11

Inhibitory

Question 12

What type of response does a Gs protein produce?

Answer 12

Activating (excitatory)

Question 13

What type of response does a Gq protein produce?

Answer 13

Activating (excitatory)

Question 14

What is the second messenger(s) that a Gi protein activates? What is the precursor to this?

Answer 14

cAMP

ATP->cAMP

Question 15

What is the second messenger(s) that a Gq protein activates? What is the precursor to this?

Answer 15

DAG + IP3

PIP2-> DAG + IP3

Question 16

What is the second messenger(s) that a Gs protein activates? What is the precursor to this?

Answer 16

cAMP

ATP->cAMP

Question 17

Which subtypes of G proteins are used for alpha 1 receptors linked to?

Answer 17

Gq

Remember: QISSQIQ- a1,a2,b1,b2,m1,m2,m3

Question 18

Which subtypes of G proteins are used for alpha 2 receptors linked to?

Answer 18

Gi

Remember: QISSQIQ- a1,a2,b1,b2,m1,m2,m3

Question 19

Which subtypes of G proteins are used for beta 1 receptors linked to?

Answer 19

Gs

Remember: QISSQIQ- a1,a2,b1,b2,m1,m2,m3

Question 20

Which subtypes of G proteins are used for beta 2 receptors linked to?

Answer 20

Gs

Remember: QISSQIQ- a1,a2,b1,b2,m1,m2,m3

Question 21

Which subtypes of G proteins are used for M1 receptors linked to?

Answer 21

Gq

Remember: QISSQIQ- a1,a2,b1,b2,m1,m2,m3

Question 22

Which subtypes of G proteins are used for M2 receptors linked to?

Answer 22

Gi

Remember: QISSQIQ- a1,a2,b1,b2,m1,m2,m3

Question 23

Which subtypes of G proteins are used for M3 receptors linked to?

Answer 23

Gq

Remember: QISSQIQ- a1,a2,b1,b2,m1,m2,m3

Question 24

What does cAMP exert most of its action through?

Answer 24

PKA (protein kinase A)

Question 25

What is the structure of PKA?

Answer 25

Two regulatory subunits and 2 catalytic subunits

Question 26

How many cAMP molecules release 2 catalytic molecules?

Answer 26

4

Question 27

What is used to maintain a low Ca2+ concentration within a cell?

Answer 27

NCX- Na+/Ca2+ exchanger (transport mechanism)

Question 28

What is used to lower the Ca2+ concentration in the cell?

Answer 28

ATP dependent mechanism- Ca2+ ATPases= PMCA and SERCA (Plasma membrane Ca2+ ATPase and Sarco/Endoplasmic reticulum Ca2+ ATPase) NCX (sodium calcium exchangers) too

Question 29

What mechanisms is used to increase the concentration of Ca2+ concentration in the cell?

Answer 29

(From extracellular environment) Voltage gated Ca2+ channels and ligand gates ion channels (From the ER/SR) Calcium induced calcium release (CICR) and IP3 receptors (IP3R)

Question 30

How does CICR work?

Answer 30

CICR is a process: an increased calcium concentration within the cytosol acts upon RYRs which release calcium from the ER/SR. calcium is the ligand which is activating the receptor.

Question 31

What receptor found on the SR/ER is involved in CICR?

Answer 31

Ryanodine receptors (RYRs)

Question 32

How do IP3Rs work to increase calcium concentration in the cytosol?

Answer 32

When a Gq protein is activated, it activates phospholipase C which causes a conformational change in PIP2 molecules, these dissociate into IP3 and DAG molecules. The IP3 then interacts with the IP3 receptor on the SER membrane causing calcium release

Question 33

What does phospholipase C do?

Answer 33

Causes a conformation change of the PIP2 molecules to produce IP3 and DAG

Question 34

Describe how inotropy in the heart is increased

Answer 34

beta 1 receptors are activated by adrenaline/noradrenaline Beta 1 receptors interacts with Gs protein Gs protein activates adenylyl cyclase Adenylyl cyclase converts ATP to cAMP cAMP activates cyclic AMP dependent protein kinase PKA phosphorylates voltage gates ion channels Ion channels open Ca2+ floods into cardiac cell Increased Ca2+ concentration in cell activates CICR pathways therefore overall increased calcium concentration in the heart cell means an increased forced of contraction (inotropy)

Question 35

Where do you find B1 receptors?

Answer 35

Heart

Question 36

Where do you find B2 receptors?

Answer 36

Lungs

Question 37

Where do you find M2 receptors?

Answer 37

Heart

Question 38

Where do you find M3 receptors?

Answer 38

Lungs

Question 39

Where do you find A1 receptors?

Answer 39

Smooth muscles in blood vessels

Question 40

Where do you find A2 receptors?

Answer 40

Smooth muscles in blood vessels

Question 41

Where do you find M1 receptors?

Answer 41

Exocrine/secretory glands