Pharmacology - Catalytic & Nuclear Receptors

Question 1

What are catalytic receptors made out of?

Answer 1

cell-surface proteins, usually dimeric in nature, which encompass ligand binding and functional domains typically in one polypeptide chain

Question 2

What does dimerisation lead to?

Answer 2

activation

Question 3

Define dimerisation in receptor:

Answer 3

a general mechanism to increase binding site affinity, specificity, and diversity

Question 4

RTK

Answer 4

Receptor Tyrosine Kinase

Question 5

Name Receptors for growth factors:

Answer 5

Epidermal growth factor- EGF
Vascular endothelial growth factor-VEGF
Insulin
Neurotrophins
Insulin-like growth factor- IGF
Platelet-derived growth factor- PDGF
& many others

Question 6

What does activation of receptor lead to?

Answer 6

cell proliferation, differentiation, survival and metabolism

Question 7

What doe HYPERactivation lead to?

Answer 7

to polyps, tumour and cancer

Question 8

Growth factor binding RTK, leads

Answer 8

dimerization and autophosphorylation

Question 9

One tyrosine kinase ______ autophosphorylation of its partner and vice versa

Answer 9

activate

• Signalling proteins recruited to RTK
• Signalling proteins contains SH2 domain to sense and bind specific RTK (specificity)

Question 10

once ligand binds to receptor [extracellular] =

Answer 10

dimerisation > autophosphorylation > activation of downstream signalling [mostly intracellular]

Question 11

Some SH2 domain proteins are enzymes

Answer 11

directly produce signals: e.g. phospholipase C- activation leads intracellular

Question 12

Some SH2 domain proteins are adaptors

Answer 12

They link the RTK with the signalling protein
-e.g. Grb2 links between EGF receptor and SOS, a regulator of the Ras-MAP kinase pathway (will learn Ras-MAP kinase in details in the progressive years)

Question 13

Signal 1

Answer 13

proliferation

Question 14

Signal 2

Answer 14

Survival

Question 15

Receptor Tyrosine Kinase (RTK)- drugs
Very limited

Answer 15

Insulin: life saving drug (in PCL III, revisit insulin’s RTK signalling

Many neurotrophin analogues couldn’t pass through clinical trials (failures)

Monoclonal antibodies

Question 16

What are Guanynyl cyclase receptors? (Limited membrane bound)

Answer 16

single-pass transmembrane proteins activated by low intracellular calcium levels and inhibited by high intracellular calcium levels

e.g- atrial natriuretic peptide
(recollect CVS lecture 5)

-released from atria, promotes vasodilation and urinary sodium excretion

Question 17

When ligand binds to receptor [Atrial natriuretic peptide] what does GTP form?

Answer 17

GTP > cGMP > PK g > vasodilation

Question 18

Guanynyl cyclase receptors – cytoplasmic-Nitric oxide

Answer 18

Nitric oxide (NO)
- endothelium derived vasodilator factor (gasotransmitters)

Question 19

Vascular Smooth muscle:

Answer 19

1. NO stimulates cytoplasmic guanylyl cyclase
2. Elevation of intracellular [cGMP]
3. Activation of protein kinase G
4. Smooth muscle relaxation
5. PDE isoform breaks down cGMP

Question 20

Cytoplasmic & Nuclear receptors
Intracellular receptors & transcription factors

Answer 20

Ligands diffuse across membranes to intracellular receptors

Question 21

Steroidal hormonal function

Oestrogen act of Oestrogen receptor
Drug: Tamoxifen

used for which coindition?

Answer 21

breast cancer

Question 22

Intracellular receptors & transcription factors

Ligands _____ across membranes to intracellular receptors

Answer 22

diffuse

Peroxisome proliferator-activated receptors (PPARs)- transcription factor
Drugs- Glitazones (anti-diabetic)

Question 23

Journey of intracellular receptors and hormones:

Answer 23

hormone > cytosolic receptor > diffusion into nucleus/ nuclear receptor > DNA to mRNA > specific proteins > biological effects