M&R Session 6 (Lecture 6.1)

Question 1

Describe paracrine signalling.

Answer 1

1) Local mediator released into interstitium

2) Binds to receptors on cells within the local vicinity to cause effects

Question 2

Describe endocrine signalling.

Answer 2

1) Hormone released into bloodstream to act on distant cells

Question 3

What is a receptor?

Answer 3

Molecule that recognises a second molecule (ligand) or family of molecules and which in response to ligand binding brings about regulation of a cellular process.

Question 4

If a receptor is unbound, what is its state?

Answer 4

Functionally silent

Question 5

What is a ligand?

Answer 5

Any molecule that binds specifically to a receptor site.

Question 6

What is an agonist?

Answer 6

A ligand that may produce activation of a receptor

Question 7

What is an antagonist?

Answer 7

A ligand that combines with a receptor site without causing activation. Competitively competes with agonist thus not allowing agonist binding

Question 8

Compared to an enzyme, what is the affinity of a receptor for its ligand?

Answer 8

Higher usually nano or micro molar.

Question 9

How are receptors classified and sub-classified?

Answer 9

Classified according to:
Specific physiological signalling molecule (agonist) recognised

Sub-classified:
Affinity (tightness of binding) of a series of antagonists

Question 10

Give an example of an antagonist for the M1, M2 and M3 receptor subtypes?

Answer 10

M1 - Pirenzipine
M2 - Gallamine
M3 - Hexahydrosiladiphenol

Question 11

What is the difference between a receptor and acceptor?

Answer 11

Receptor:
Silent at rest
Agonist binding stimulates a biological response

Acceptor:
Operate in absence of ligand
Ligand binding alone produces no response

Question 12

Give an example of an acceptor?

Answer 12

Dihydrofolate reductase

Question 13

What are the four types of signal transduction ?

Answer 13

1) Membrane-bound receptors with integral ion channels
2) Membrane-bound receptors with integral enzyme activity
3) Membrane - bound receptors which couple to effectors through transducing proteins
4) Intracellular receptors

Question 14

Give examples of mem-bound Rs with integral ion channels.

Answer 14

nAChR
GABA R
Glycine R
NMDA, AMPA and kainate
IP3 R

Question 15

Give examples of classical and non-classical ligand gated ion channels?

Answer 15

Classical : nAChR

Non-classical : ATP sens K+ channel, P2x purinoceptor, Ryanodine receptor

Question 16

Give an example and describe a mem-bound Rs with integral enzyme activity?

Answer 16

Two alpha helices come together (dimerise) to form functional receptor with cytoplasmic catalytic domain

e.g. PDGFR
Atrial natriuretic peptide (ANP) receptor - linked directly to guanylyl cyclase (GTP&raquo_space;> cGMP)

Growth receptors (insulin, EGF, PDGF) - linked to TK

Question 17

Describe the process of signalling via TK-linked receptors.

Answer 17

1) Binding with agonist to receptor
2) Dimerisation and autophosphorylation on cytoplasmic tail by TK towards tyrosine residues
3) EITHER enzyme detects Y-P and binds to it causing the enzyme to be activated e.g. SH2 (src - homology 2 domains)

OR

3) Y-P detected by transducer e.g. domain transducers e.g. IRS-1, Grb2 which gets itself Y-P and activates enzymes

Question 18

Describe mem-bound Rs that signal through transducing proteins / 7TMD Rs? Give examples.

Answer 18

1) Coupled through G-proteins to enzymes or channels with ligands generally binding into cleft

Examples:

Adrenaline binding to Beta-adrenoceptors activates the enzyme adenylyl cyclase via G-protein Gs

Acetylcholine binding to M2 muscarinic acetylcholine receptors stimulates K+ channel opening via a different G-protein, Gi (inhibits cAMP prodn)

Question 19

Describe the intracellular receptor family.

Answer 19

1) Inhibitory protein complex blocks RNA pol from transcribing the steroid sens genes.
2) Once steroid binds to its binding site, this causes dissociation of the inhibitory complex so the DNA binding site is exposed allowing transcription,

Question 20

What are partial agonists?

Answer 20

Agonists which stimulate a receptor but are unable to elicit the maximum cell response.