7 - Transmembrane Receptors

Question 1

What are transmembrane receptors?

Answer 1

Transmembrane receptors are proteins that span the
thickness of the plasma membrane of the cell

Question 2

Where is the transmembrane receptor in relation to the cell?

Answer 2

One end of the receptor is outside (extracellular domain)
and one end is inside (intracellular domain) the cell

Question 3

What three sections of the receptor are there?

Answer 3

1. extracellular - discriminator domain with ligand binding site
2. transmembrane - transmembrane domain
3. intracellular - effector domain

Question 4

What three types of transmembrane receptors are there?

Answer 4

1. protein kinase-coupled receptor
2. G-protein-coupled receptor
3. ion channel-coupled receptor

Question 5

What effector domains do the three transmembrane receptors have?

Answer 5

1. protein kinase-coupled receptor - 2 PK domains
2. G-protein-coupled receptor - G protein
3. ion channel-coupled receptor - none

Question 6

What are drugs?

Answer 6

Drugs are receptor modulators and do not confer
new properties on cells and tissues

Question 7

What can drugs do?

Answer 7

Drugs can enhance, diminish or block the generation,
transmission or receipt of a ligand-generated
signal by several mechanisms

Question 8

How is the action of a drug classified?

Answer 8

The action of a drug is classified according to whether
it produces (agonist) or diminishes (antagonist)
the signal

Question 9

What are the action pathways of drugs on receptors?

Answer 9

1. input signal activates the ANTAGONIST, which interacts with the discriminator domain of the receptor, which is attached for the effect domain
2. input signal activates the AGONIST, which interacts with the discriminator domain of the receptor, which is attached for the effect domain
   - there is a highly specific, non covalent interaction according to the lock-key principle (structural complementarity)
   - this may affect various signalling pathways
   -output signals are generated

Question 10

What drugs antagonise. block, or inhibit endogenous proteins? (6)

Answer 10

• Antagonists of Cell Surface Receptors
• Antagonists of Nuclear Receptors
• Enzyme Inhibitors
• Ion Channel Blockers
• Transport Inhibitors
• Inhibitors of Signal Transduction Proteins

Question 11

What drugs activate endogenous proteins?

Answer 11

• Agonists of Cell Surface Receptors
• Agonists of Nuclear Receptors
• Enzyme Activators
• Ion Channel Openers

Question 12

How do drugs use sites on the receptor? (agonists and antagonists, allosteric agonists and antagonists, and other drugs)

Answer 12

1. Agonists and antagonists compete with
   hormones/neurotransmitters for binding sites
2. Allosteric agonists or antagonists enhance or
   block the signal by binding to allosteric sites
   that influence signal transmission
3. Other drugs can block signal transduction
   within the membrane or at intracellular signal
   reception points

Question 13

What mechanisms are used for the recognition of a drug or hormone by a receptor?

Answer 13

The recognition of a drug or hormone by a receptor
uses non-covalent mechanisms, such as hydrogen
bonds, electrostatic forces, hydrophobic and Van der
Waals forces

Question 14

What chemical bonds are involved in drug actions (from strongest of weakest)?

Answer 14

1. covalent
2. ionic
3. hydrogen
4. hydrophobic
5. van der Waals

Question 15

Properties of most drug-receptor interactions

Answer 15

• reversible
• weak chemical bonds

Question 16

Properties of irreversible drug-receptor interactions

Answer 16

• not common
• strong chemical bonds (covalent)
• e.g. aspirin, anti-tumour drugs
• usually undesirable
• reversal of effects/toxicity
• mutagenicity/carcinogenicity

Question 17

What four methods are used for studying cell signalling pathways>

Answer 17

1. activation
2. inhibition
3. interaction
4. cellular localisation

Question 18

What is involved in the ACTIVATION method for studying cell signalling pathways?

Answer 18

• activator
• constitutively active mutant transgene

Question 19

What is involved in the INHIBITION method for studying cell signalling pathways?

Answer 19

• inhibitor
• dominant-negative mutant
• anti-sense mRNA
• siRNA
• gene knockout

Question 20

What is involved in the INTERACTION method for studying cell signalling pathways?

Answer 20

• co-immunoprecipitation
• yeast two-hybrid system
• fluorescence resonance energy transfer (FRET)

Question 21

What is involved in the CELLULAR LOCALISATION method for studying cell signalling pathways?

Answer 21

• cell fractionation
• immunohistochemistry
• GFP tagging