Chronic receptor modulation

Question 1

What are Micro RNAs (miRNAs)

Answer 1

19-24 nucleotides longDouble strandedEnables sequence-specific inhibition.They are highly stable and transported between cells by microvesicles)

Question 2

Define deactivation

Answer 2

Loss of gating by removal of activation signal (ligand or voltage)(signal gone; response stops)

Question 3

Define desensitisation

Answer 3

Loss of gating after activation signal is removed. (response continues even when signal has gone)

Question 4

Explain desensitisation in the context of the 5-HT receptors in guinea pigs

Answer 4

Response is lost after prolonged exposure to 5-HT. This is not because of endocytosis of the receptor.5-HT is moved into cells and is slowly released. This prevents desensitisation recovery (though cannot cause desensitisation on its own) - Resensitisation is blocked by low levels of 5-HT

Question 5

What is palonosetron and how does it work

Answer 5

It inhibits 5-HT3 receptors (pseudo-permanent antagonist). Has high affinity for the receptors. Used in radiotherapy and chemotherapy-induced emesis. Receptors can recover, but by replacement of receptors with new [unbound] receptors.

Question 6

How does the GABAa receptor undergo endocytosis

Answer 6

Clathrin and AP (adaptor protein) 2 complex mediates endocytosis. This is to regulate the number of receptors available at the cell surface.

Question 7

Where are GABAa receptors usually delivered to/removed from

Answer 7

Extrasynaptic sites

Question 8

What does LTP stand for

Answer 8

Long Term Potentiation

Question 9

What are the causes of early phase LTP

Answer 9

Phosphorylation and trafficking

Question 10

Give some examples of RNA modification

Answer 10

DeaminaseGluR2 editing (of the gene RNA)

Question 11

What are pharmacological chaperones

Answer 11

Secreted transmembranal proteins. Found in ER, Goigi, Lysosomes, Surface.

Question 12

Give some examples of pharmacological chaperones found in the ER

Answer 12

CalnexinProtein disulphide isomerases (PDI)BiP

Question 13

Give some examples of co-translational process in the ER

Answer 13

Protein glycosylationDisulphide bond formationProtein folding and oligomerisation

Question 14

What do glycosylated proteins have to do to get out of the ER

Answer 14

One step - requires glucose removal. Policed by calnexin (pharma chaperone)

Question 15

Why is disulphide bond formation important

Answer 15

Occurs co-translocationallyImportant for forming tertiary structureChaperone = Protein disulphide isomerases (PDI)

Question 16

What role do Calnexin and BiP have in RNA modifications

Answer 16

Act on immature proteins.Specifically on Monoglucosylated sugars (calnexin) and Hydrophobic domains (BiP). Fixes up the protein just before it leaves the ER to go into the cytoplasm.

Question 17

What is KDEL

Answer 17

Present in ER and Golgi. Includes BiP, Calnexin and PDI

Question 18

What are assembly signals

Answer 18

Intracellular signals that drive subunit-subunit interactions. (in receptors). Highly conserved

Question 19

Give some examples of chemical chaperones

Answer 19

GlycerolDMSOLow temperature? (slows processes down so higher success rate)

Question 20

What is bicuculline

Answer 20

A competitive antagonist of the GABA receptor