L4: Receptors

Question 1

What are the three main groups of receptors?

Answer 1

1. plasma membrane receptors
2. intracellular receptors
3. nuclear receptors

Question 2

What are nuclear receptors and how do they become active?

Answer 2

• examples: estrogen receptors and retinoic acid receptors
• contain zinc fingers and usually need to dimerize to become active
• at rest, they sit on the outside of the nucleus in the cytosol. When agonist activates them, they dimerize & enter nucleus to interact with DNA.

Question 3

What are intracellular receptors and how are they activated?

Answer 3

• examples: ryanodine and IP3 receptors
• activated by specific ligands or modulators:
• Ryanodine receptors activated by calcium & other modulators & act as ligand-gated calcium channels
• IP3 receptors activated by second messenger IP3 & also function as ligand-gated calcium channels

Question 4

What are the three main families of plasma membrane receptors?

Answer 4

1. Ligand-gated ion channels: Includes receptors like nACh, 5HT3, GABAa, glycine, and ZAC, as well as ATP-like receptor (P2X) & ionotropic glutamate-like receptors (AMPA, NMDA, kainite).
2. G-protein linked receptors: Includes receptors with 7 transmembrane domains, like rhodopsin-like receptors & metabotropic glutamate-like receptors.
3. Intrinsic enzyme receptors: Includes receptor tyrosine kinases (e.g., insulin receptor) and receptor guanylate cyclase (e.g., atrial natriuretic peptide receptor).

Question 5

Give examples of receptors in the ligand-gated ion channels family

Answer 5

1. nACh - nicotinic acetylcholine receptor
2. 5HT3 - serotonin type 3 receptor
3. GABAa - gamma-aminobutyric acid type A receptor
4. Glycine receptor
5. ZAC receptor
6. P2X receptor (ATP-gated ion channel)
7. Ionotropic glutamate receptors (AMPA, NMDA, kainite)

Question 6

What are the characteristics of G-protein linked receptors?

Answer 6

• They have 7 transmembrane domains.
• They can be rhodopsin-like receptors or metabotropic glutamate-like receptors.

Question 7

Name examples of G-protein linked receptors.

Answer 7

Rhodopsin-like receptors
Metabotropic glutamate-like receptors

Question 8

What are intrinsic enzyme receptors?

Answer 8

They are receptors that act as enzymes themselves upon ligand binding

Question 9

Give examples of intrinsic enzyme receptors.

Answer 9

1. Receptor tyrosine kinases (e.g., insulin receptor)
2. Receptor guanylate cyclase (e.g., atrial natriuretic peptide receptor)

Question 10

How do pharmacologists define receptors?

Answer 10

• based on their signalling mechanism
• Muscarinic acetylcholine receptors are G-protein coupled
• nicotinic acetylcholine receptors are ionotropic
• P2X receptors are ion channels on which ATP acts
• P2Y receptors are G-protein coupled
• intrinsic enzyme receptors can be either tyrosine kinases (e.g., insulin and nerve growth factor receptors) or atrial natriuretic peptide receptors (guanylate cyclase-linked).

Question 11

Where can receptors be located in a cell?

Answer 11

intracellularly or on the plasma membrane

Question 12

What structural element can help identify a DNA binding receptor?

Answer 12

Zinc fingers can help identify a DNA binding receptor

Question 13

Which receptors are located on intracellular cell membranes?

Answer 13

• Ion channels
• G-protein coupled receptors
• kinase receptors

Question 14

Describe the structure of the following ligand-gated ion channel: Nicotine-like receptors

Answer 14

• Consist of 5 subunits, each made up of 4 domains
• The N and C loops are located extracellularly, with the ligand-binding site (LBS) on the N loop
• ion pore is on the second domain.

Question 15

Describe the structure of the following ligand-gated ion channel: ATP-P2X receptor

Answer 15

• Composed of 3 subunits, each made up of 2 transmembrane domains.
• has a large extracellular loop with the LBS, and short intracellular N and C terminals
• ion pore is made up of the second domain.

Question 16

Describe the structure of the following ligand-gated ion channel: Ionotropic glutamate receptors

Answer 16

• Comprise 4 subunits with 3 intracellular domains
• have a long extracellular N terminal with the LBS and short intracellular C terminal
• ion pore is located between the first and second domain

Question 17

What are the main families of GPCRs?

Answer 17

Rhodopsin-like and Metabotropic Glutamate receptor-like.

Question 18

Identify the steps required for the activation of an intrinsic enzyme receptor.

Answer 18

• ligand binding
• dimerization
• autophosphorylation
• target phosphorylation.

Question 19

How are receptors targeted to different parts of a cell?

Answer 19

• through sorting sequences in subunits, which direct them to their specific targets

Question 20

Describe the steps involved in the binding of ligand to the receptor and activation of G-proteins.

Answer 20

1. Ligand binding increases affinity of the receptor for the C terminus to the 3rd intracellular loop of the receptor, leading to the binding of the G protein to the G protein region.
2. This binding results in the removal of GDP and binding of GTP to the G protein, leading to the activation of the G protein.
3. The alpha subunit of the G protein separates from the betagamma subunit and moves into the cytosol.
4. The betagamma subunit tends to stay close to the membrane as it is lipidated.
5. The activity of the G protein is stopped by its GTPase activity, which hydrolyzes GTP to GDP

Question 21

What determines the speed of GTPase activity in G-proteins?

Answer 21

• can vary and depends on the effector and other regulators, such as RGS (Regulators of G-protein Signalling)

Question 22

Name the families of G-proteins and their respective alpha subunits.

Answer 22

1. Gs family - includes alphas and alphaolf.
2. G1 family - includes alphail, alphai2, alphai3, alphaoA, alpha0B, alphaz, alphat.
3. Gq family - includes alphaq, alpha11, alpha14, alpha15, alpha16.
4. G12 family - includes alpha12, alpha13.

Question 23

What are some actions of the betagamma subunit of G-proteins?

Answer 23

• can activate kinases that mediate receptor desensitization
• inhibit calcium channels (particularly Go proteins)
• activate potassium channels
• regulate other free alpha subunits