Signal Transduction

Question 1

Give an agonist of beta-2 adrenoceptors.

Answer 1

Anti-asthma
Salbutamol
Salmetenol

Question 2

Give an agonist of a mu-opioid receptor.

Answer 2

Analgesic
Morphine
Fentanyl

Question 3

Give an antagonist of beta adrenoceptors

Answer 3

Hypertension treatments
Propanolol
Atenolol

Question 4

Give an antagonist of D2 dopamine receptors

Answer 4

Neuroleptics e.g. anti-schizophrenics
Haloperidol
Sulpinide

Question 5

What mutation gives rise to nephrogenic diabetes insipidus?

Answer 5

Loss of function mutation to V2 vasopressin receptor

Question 6

Describe the general structure of GPCR proteins.

Answer 6

One polypeptide chain
7 transmembrane domains
Extracellular N terminus
Intracellular C terminus

Question 7

Where can ligands bind to a GPCR?

Answer 7

Between the transmembrane domains or on a specialised N-terminus

Question 8

What governs the magnitude of the signal passed on from a GPCR?

Answer 8

A timer system in the GPCR

Cellular regulation of GTPase

Question 9

What G-protein alpha subunit is associated with a beta-adrenoceptor?

Answer 9

Gs

Question 10

What G-protein alpha subunit is associated with an alpha-2 adrenoceptor?

Answer 10

Gi

Question 11

What G-protein alpha subunit is associated with an alpha-1 adrenoceptor?

Answer 11

Gq

Question 12

What G-protein alpha subunit is associated with the M2 and M4 muscarinic receptors?

Answer 12

Gi

Question 13

What G-protein alpha subunit is associated with the M1 and M3 muscarinic receptors?

Answer 13

Gq

Question 14

How does cholera toxin affect G-proteins?

Answer 14

Eliminates GTPase activity on Gs-alpha which makes it irreversibly activated

Question 15

How does pertussin toxin affect G-proteins?

Answer 15

Interferes with GDP/GTP exchange on Gi-alpha so it becomes irreversibly activated

Question 16

What is the function of adenylyl cyclase?

Answer 16

ATP to cAMP

Question 17

What is the function of phospholipase C?

Answer 17

PIP2 to IP3 and DAG

Question 18

What is the function of phosphoinositide-3-kinase (PI3K)

Answer 18

PIP2 to PIP3 (thought to be a survival signal)

Question 19

What is the function of cGMP phosphodiesterase?

Answer 19

cGMP to 5’GMP

Question 20

Give two effectors linked to G-proteins which are ion channels.

Answer 20

Voltage-operated calcium channels (VOCC)

G-protein regulated inwardly-rectifying K+ channels (GIRKs)

Question 21

Give an example of a Gs coupled receptor

Answer 21

Beta adrenoceptors
D1 dopamine receptors
H2 histamine receptors

Question 22

Give an example of a Gi coupled receptor

Answer 22

Alpha-2 adrenoceptors
D2 dopamine receptors
Mu-2 opioid receptors

Question 23

What enzyme does cAMP exert the majority of it’s action on and how?

Answer 23

Protein kinase A
cAMP binds the regulatory subunits which sit in the enzyme site, allowing the catalytic subunits to dissociate, allowing full activity.

Question 24

What effect does activation of an Gq coupled receptor have on a cell?

Answer 24

Activates phospholipase c which cleaves PIP2 to DAG (in the membrane) and IP3 (in the cell)
IP3 then activates IP3 receptors in the ER which are calcium channels, increasing the release of calcium.
DAG and the extra calcium activate protein kinase C which has it’s own specific intracellular targets.

Question 25

Give an example of a Gq coupled receptor

Answer 25

Alpha-1 adrenoceptors M1 muscarinic receptors H1 histamine receptors

Question 26

Where does the most significant signal amplification begin to happen?

Answer 26

After enzyme activation

Question 27

Describe how activation of specific GPCRs in the heart causes positive ionotropy.

Answer 27

Adrenaline or noradrenaline activate B1 adrenoceptors. This allows cAMP formation by adenylyl cyclase. cAMP activates PKA which phosphorylates targets, one of which is VOCC in the membrane. This increases calcium concentration in the cell and therefore contractility.

Question 28

Describe how vasoconstriction is initiated by noradrenaline.

Answer 28

Interacts with alpha-1 adrenoceptors which increases calcium concentration and protein kinase C activity by Galpha q. This causes increased contractility

Question 29

Describe how acetylcholine can cause bronchoconstriction.

Answer 29

ACh binds to M3 muscarinic receptors.

Question 30

How is neurotransmitter release modulated, using the example of morphine?

Answer 30

Morpine activates a mu-opioid receptor, which allows the dissociation of the beta-gamma subunit. This inhibits N-type VOCC, reducing calcium influx and therefore lowering neurotransmitter release. This is modulating rather than inhibiting.

Question 31

Why is cell context important when discussing the action of GCPRs?

Answer 31

There is cell background specificity as the cellular components determine the exact effects, but in a specific cell the changes on activation will be hard-wired.