M&R Session 7 (Lecture 7.1)

Question 1

What are the 3 ‘superfamilies’ of cell-surface receptor?

Answer 1

1) Ligand-gated e.g. nAChR
2) Receptors with intrinsic enzymatic activity e.g. receptor TKs e.g. Insulin R
3) GPCR e.g. mAChR

Question 2

Give examples of agonists that activate Beta-2 adrenoceptors for asthma treatment, and Mu opioid receptors for analgesia?

Answer 2

Beta 2 - salbutamol, salmeterol

Mu opioid - morphine, fentanyl

Question 3

Give examples that antagonise Beta adrenoceptors for hypertension and D2 dopamine Rs for schizophrenia?

Answer 3

Beta - propranolol, atenolol

D2 - Haloperidol, sulpride

Question 4

List 3 diseases associated with signal transduction. Say what has been lost/gained in function?

Answer 4

1) Retinitis pigmentosa - loss of function to rhodopsin
2) Nephrogenic DI - LOF to the V2 vasopressin receptor
3) Familial male precocious puberty - GOF to LH R

Question 5

What substances to GPCR respond to?

Answer 5

1) Ions - H+, Ca2+
2) NTs - ACh, Glu
3) Peptide and non-peptide hormones - glucagon, adrenaline
4) Large glycoproteins - TSH

Question 6

What is the general structure of a GPCR?

Answer 6

Single PP chain
7TM spanning regions
Extracellular N-termini
Intracellular C-termini

Question 7

What are the two regions that a ligand can bind on the GPCR?

Answer 7

1) TM 2-3 regions e.g. ACh

2) N-terminal region e.g. Glutamate

Question 8

What does the ‘G’ in G-protein stand for?

Answer 8

Guanine nucleotide binding

Question 9

What are the three subunits of GPs?

Answer 9

G alpha
G beta
G gamma

Question 10

Describe the process if an agonist binds to a GPCR?

Answer 10

1) GPCR binds agonist
2) GPCR interacts with GP heterotrimer with GDP bound
3) GDP is released and GTP binds releasing the heterotrimer from the GPCR.
4) GTP binding causes dissociation of the heterotrimer into G alpha and G beta-gamma
5) The subunits can interact with effector proteins( second messenger-generator enzymes or ion channels)
6) The G alpha has intrinsic GTPase activity that hydrolyses GTP&raquo_space; GDP slowly.
7) The two distinct sunbunits come together to form the original heterotrimer once the G alpha has GDP bound to it.

Question 11

What are G alpha S subunits i) ligands activation, ii) GPCR and what do they activate ?

Answer 11

i) Adrenaline/Noradrenaline
ii) Beta adrenoceptor
iii) Activates adenylyl cyclase (ATP&raquo_space; cAMP)

Question 12

What are G alpha I subunits i) ligands activation, ii) GPCR and what do they activate ? (for Adr + ACh)

Answer 12

i) Adrenaline/Noradrenaline
ii) Alpha 2 adrenoceptor
iii) Inhibit AC (increase K+ conductance so hyperpolarise membrane)

FOR ACh:

i) ACh
ii) M2/M4 receptor
iii) “”

Question 13

What are G alpha Q subunits i) ligands activation, ii) GPCR and what do they activate ? (for Adr + ACh)

Answer 13

i) Adrenaline/Noradrenaline
ii) Alpha 1 adrenoceptor
iii) Activates Phospholipase C

FOR ACh:

i) ACh
ii) M1/M3 receptor
iii) “”

Question 14

What are G alpha T subunits i) ligands activation, ii) GPCR and what do they activate ?

Answer 14

i) Light
ii) Rhodopsin
iii) Acitvates cyclic GMP phosphodiesterase

Question 15

Which bacterium releases Cholera toxin?

Answer 15

Vibrio cholerae

Question 16

Which bacterium releases pertussis toxin?

Answer 16

Bordetella pertussis

Question 17

What is the result of ingesting cholera or pertussis toxin ?

Answer 17

Cholera - severe dehydration by watery faeces

Pertussis - Violent coughing aka whooping cough - difficult to breathe

Question 18

How do cholera and pertussis interfere with G proteins function?

Answer 18

CTx and PTx are enzymes that ADP-ribosylate G proteins

CTx:
Eliminates GTPase activity of Gs alpha ( GsA becomes irreversibly activated)

PTx:
Interferes with GDP/GTP exchange on GiA (GiA becomes irreversibly inactivated)