Ligand - recepto interaction

Question 1

Cell surface receptors are ….. that are designed to recognise and respond to specific transmitter molecules aka …

Answer 1

proteins, ligands

Question 2

Name the 2 types of cell surface receptors?

Answer 2

Ionotropic (Ion linked Channels)
Metabotropic (G-protein linked)

Question 3

For Ion-channel linked (ionotropic) give:
. an example
. 1 sentence explaination of how they elicit a response
. Time scale

Answer 3

Ion-channel linked (ionotropic)

nAchR

Result in changes in membrane potential or ionic concentrations within the cell

Time scale - milliseconds

Question 4

For G-protein linked (metabotropic) give:
. an example
. 1 sentence explaination of how they elicit a response
. Time scale

Answer 4

G-protein linked (metabotropic)

mAchR, α and β adrenoceptors

Protein phosphorylation -> Calcium release or change in excitability

Question 5

Name the Three types of GPCRs

Answer 5

Gs - stimulatory

Gi - inhibitory

Gq

Question 6

State the generic mechanism of action of G proteins and 1 short sentence about the termination of signalling

Answer 6

Mechanism of activation

At rest the αβγ timer disassembled from the receptor with GDP bound to α

Ligand binding causes trimer to bind to receptor

GDP exchanged for GTP

Active forms of G protein (α-GTP and βγ) released and interact with targets

Termination of signalling = hydrolysis of GTP

Question 7

Enzyme linked receptors (kinase) - recall

Answer 7

Protein and receptor phosphorylation, guanylate cyclase activity

Influence gene expression

Time scale - hours

Question 8

Ligand-receptor interactions - terminology
affinity & efficacy - define

Answer 8

Affinity = chemical forces involved in the association of a drug with the receptor

Efficacy = ability of a drug to activate the receptor and produce a response

Question 9

Potency versus efficacy -
effect on concentration & response

Answer 9

Potency - same response different conc

Efficacy - same conc different response

Question 10

Agnoists versus antagonists - 2 lines def

Answer 10

Agonists are drugs that combine with receptors to produce a response

Antagonists are drugs that combine with receptors without producing a response (no efficacy)

Question 11

Types of antagonist

Answer 11

Competitive - bind to the same site as the endogenous agent, reversible and overcome by a higher concentration of agonist

Can have irreversible competitive agonists which bind to the binding site permanently, reducing the maximum response that can be achieved by the agonist. The antagonistic action will also increase with exposure time as more of the binding sites become irreversibly bound to antagonists.

Non-competitive - bind to an allosteric site, changing the tertiary structure of the receptor, reducing its affinity for the agonist. Effects cannot be reversed by increasing the agonist concentration

Question 12

Ligand-receptor interactions

Proteins can be receptors, they are cellular macromolecules that respond to chemical signals of varying kinds

Receptors are signal transducing proteins that change conformation with an agonist binding, but doesn’t change the agonist itself

Question 13

Name the 3 Types of cell-surface receptor:

Answer 13

• ligand-gated ion channels (ionotropic)
• G-protein linked receptors (metabotropic)
• Enzyme-linked receptors

Question 14

Ligand-gated ion channels (ionotropic):

Recall & Read

Answer 14

When a specific ligand binds to the receptor, the ion channel will open for a short period of time

Allows for changes in membrane potential and intracellular ion concentration

Example is nAChRs, glycine receptors, GABA receptor

Very short response- within milliseconds

Question 15

G-protein linked receptors (metabotropic)
Recall & Read

Answer 15

Ligand binds to 7 transmembrane domain proteins creates a shift in the C-terminus- changes associated heterotrimeric G-protein

⍺-subunit dissociates with GTP molecule and then βγ-subunits dissociate as well

As long as ligand remains bound, multiple G-proteins can follow this process

Response can last from seconds to a few minutes

Question 16

Enzyme-linked receptors:
Recall & Read

Answer 16

When ligand binds, they often dimerise and transphosphorylate their enzymatic domains so they can act intracellularly on second messengers to create different cascade responses

Can frequently lead to changes in transcription and gene expression

Action has a delay of a few hours but very long-lasting effects

Question 17

Agonist
Full, Partial & inverse agonist definition

Answer 17

Full agonist: can stimulate maximum response with a high enough concentration- efficacy of 1

Partial agonist: can stimulate a response but it plateaus with maximum concentration before a maximal response is achieved
Inverse agonist: binds to receptor and causes conformational change which decreases its activity

Question 18

Antagonist - Recall & Read

Answer 18

Antagonist: can block the receptor site without stimulating a response which reduces signalling and prevents the receptor being stimulated

Competitive antagonist: binds at same site as ligand- can be combatted with increased ligand conc

Non-competitive antagonist: binds at allosteric site which leads to a conformational change stopping the ligand from binding