Intercellular signalling pathways (2)

Question 1

Give examples of proteins involved in the GPCR pathway

Answer 1

• Adenylyl cyclase
• Phospholipase C
• PI3K
• cGMP Phosphodiesterase
• VOCCs
• GIRKs
• Ion Channels

Question 2

What is the function of Adenylyl Cyclase?

Answer 2

Converts ATP to cAMP which will bind to PKA

Question 3

Give examples of GPCRs that stimulates adenylyl cyclase

Answer 3

• Gs - coupled receptors
• B-adrenoreceptors
• D1-dopamine receptors
• H2-histamine receptors

Question 4

Give examples of GPCRs that inhibit Adenylyl cyclase

Answer 4

• Gi coupled receptors
• alpha2-adrenoreceptors
• D2-dopamine receptors
• mu-opiod receptors

Question 5

What does the R and C resemble on PKA

Answer 5

R : regulatory

C : catalytic

Question 6

Describe the characteristics of PKA

Answer 6

• contains 2 catalytic and 2 regulatory units
• cAMP binding spot on regulatory units

Question 7

State the function of cAMP

Answer 7

• Binds to regulatory units of PKA
• PKA undergoes confirmational change
• Catalytic subunits liberated and active

Question 8

State the function of PKA

Answer 8

Phosphorylates proteins and enzymes in cytoplasm

Question 9

State the function of Phospholipase C

Answer 9

PLC catalyses cleavage of PIP2 into IP3 and DAG

Question 10

Is DAG an intrinsic protein?

Answer 10

Yes

Question 11

State the fucntion of IP3 un relation to [Ca2+]

Answer 11

• Binds to IP3 receptor on ER which causes Calcium to be released from ER lumen into cytoplasm
• Increases cytoplasmic Ca2+ con by 5-10 folds
• [IP3] in cell can be rapidly increased by Gq proteins and growth factors

Question 12

Give examples of GPCRs that stimulate PLC

Answer 12

• Gq-coupled receptors
• alpha1-adremoreceptors
• M1-muscuranic receptors
• H1-histamine receptors

Question 13

What does GPCR pathway give rise to?

Answer 13

Signap Amplification

Question 14

Give an example of clinical scenario where adrenaline/noradrenaline acts on B1-adrenoreceptors and effects Adenylyl cyclase

Answer 14

Inotropy in the heart

Question 15

Describe the signalling pathway that causes Inotropy in the heart

Answer 15

• Adrenaline/noradrenaline binds to B1-adrenoreceptors
• Adenylyl cyclase stimulated - ATP to cAMP
• cAMP activates PKA
• PKA binds and activates VOCC
• VOCC open, Ca2+ diffuse into cytoplasm
• Increase [Ca2+], Increase force of heart contraction

Question 16

Give examples of hormones and receptors that causes smooth muscle contraction

Answer 16

• Noradrenaline/adrenaline - alpha1-adrenoreceptors on vascular smooth muscle - vasoconstriction
• acetylcholine - M3-muscarinic receptors on bronchiolar smooth muscle - bronchoconstriction
• All muscle contraction utilise Gq - PLC - IP3/Ca2+, DAG/PKC pathways

Question 17

What type of GPCR modulates neurotransmitter release?

Answer 17

presynaptic GPCR

Question 18

Give an example of presynaptic GPCR and a ligand. Describe their pathway.

Answer 18

• mu-opiod receptor, morphine
• morphine binds to mu-opioid receptors
• yB subunit dissociates from g protein and binds to VOCC
• yB inhibits VOCC
• Ca2+ unable to diffuse into cytoplasm

Question 19

What is the effect of inhibition of VOCC by yB subunit?

Answer 19

• Reduces Ca2+ influx
• reduces neurotransmitter release

Question 20

State the characteristics of signal transduction in biological membranes

Answer 20

• Diverse : diverse range of stimuli, receptors and Gproteins
• Specific : specific ligand-receptor interactions
• Amplification : Allow small changes in extracellular signals to elicit significant changes in cellular behavior