intracellular receptors

Question 1

What type of ligand will interact with a receptor in the nucleus or cytoplasm?

Answer 1

a small hydrophobic ligand which can diffuse across the membrane

Question 2

What are the three examples of intracellular ligands we studied?

Answer 2

1. steroid hormones
2. nitric oxide
3. auxin

Question 3

what does nitric oxide bind to in a cell?

Answer 3

Binds to soluble guanylate cyclase. (receptor itself is enzyme)

Question 4

What type of cell will a nitric oxide signal be perceived in, after it has been released from an endothelial cell?

Answer 4

smooth muscle cell lining blood vessels.

Question 5

What effect does nitric oxide entering a cell, and therefore intracellular cGMP levels increasing, have overall?

Answer 5

Nitric oxide entering the cell, stimulating soluble guanylate cyclase and increasing intracellular cGMP will cause the muscle to relax (by stimulating protein kinase G which decreases intracellular calcium levels) - blood vessel will expand and blood flow will increase.

Question 6

What is the direct action of protein kinase G?

Answer 6

Protein kinase G inhibits calcium channels and IP3 receptors.
Activates MLC phosphatase which inhibits actomyosin.

Question 7

How is nitric oxide signaling pathway turned off?

Answer 7

in the smooth muscle cell, nitric oxide signaling turned off by PDE5 phosphodiesterase, converting cGMP back to GMP (hydrolysis reaction)

Question 8

how was nitric oxide signaling discovered?

Answer 8

Acetylcholine was applied to blood vessels. This caused them to contract as expected.
however, the addition of Ach to lumen of small isolated blood vessels caused them to contract asw (unexpected)
This lead them to think relaxation of lumen depended on presence of endothelial cell.
Called it endothelium relaxing factor
saw that it had the same spectral shift as nitric oxide when added to haemoglobin

Question 9

How can nitric oxide signaling be used medically to treat erectile disfunction?

Answer 9

naturally, nitric oxide release in the nerve terminals of the penis cause localised increased blood flow and therefore cause an erection. 
Sildenafil citrate (Viagra) is a reversible inhibitor of PDE5. prevents inhibition of nitric oxide pathway

Question 10

What is another medical use of sildenafil citrate?

Answer 10

can be used to treat pulmonary hypertension and cardiac hypertrophy

Question 11

Where would the nitric oxide signaling pathway have an affect if someone was at a high altitude?

Answer 11

At high altitude there is oxygen deprivation. Blood vessels will dilate to increase blood flow (triggered by nitric oxide pathway)

Question 12

Why might HDL cholesterol be administered in a medical setting?

Answer 12

HDL cholesterol can stimulate nitric oxide production.

Dilates blood vessel to help prevent ischemia and angina

Question 13

How are steroid hormones transported in the blood?

Answer 13

via carrier proteins

Question 14

what are the key features of the cytosolic receptors for steroid hormones?

Answer 14

Lipophilic and can diffuse across a membrane

Question 15

Describe the basic (very basic) pathway of steroid hormone signal transduction.

Answer 15

Hormone carried in blood by carrier protein
Secreted into target cell, diffuses across membrane
Hormone interacts with cytosolic receptor causing hormone/receptor complex to form
Hormone receptor complex will translocate into nucleus and alter expression of target gene

Question 16

What specific region of DNA do hormone/receptor complexes bind to?

Answer 16

Steroid hormone receptors bind to DNA response elements

Question 17

What are the three key regions of the general primary structure of a nuclear receptor are found in all?

Answer 17

variable regions (0 AA identity), DNA binding region (42-94% AA identity) and ligand binding domain (15-57% identity)

Question 18

How long will a hormone induced response last?

Answer 18

Can last from hours to days

Question 19

What are the key features of the steroid response element?

Answer 19

6bp inverted repeats
separated by 3bp
receptor binds as a dimer (homo)

Question 20

What are the key features of a direct repeat element?

Answer 20

Directs repeats.

Receptor binds as heterodimer with RxR

Question 21

What type of receptor binds direct repeat elements?

Answer 21

receptors for thyroxine and retinoic acid

Question 22

How do steroid receptors and retinoic acid receptors bind their ligands differently?

Answer 22

Steroid receptors bind their ligand in the cytoplasm of the target cell. They translocate to the nucleus as a complex and bind inverted repeat elements.
Retinoic acid binds its receptor in the nucleus.
The receptor interacts with RxR to form a heterodimer and binds direct repeat elements.

Question 23

How do both inverted repeat elements and direct repeat elements become modified by receptor binding?

Answer 23

They both receive epistatic modifications from receptor binding

Question 24

How specifically do the two different receptors modify their repeat elements?

Answer 24

Steroid receptor binding to IRE enhances Histone acetyl transferases (increase open chromatin state, increase levels of transcription)
Receptors binding direct repeat elements inhibit Histone Deacetylases (inhibit closing chromatin by removing acetyl modifications, increased levels of transcription)