Session 6 - Drug Targets: The Receptors K(L)ING and GPCRs

Question 1

Define a receptor

Answer 1

A receptor is a molecule that recognises specifically a second molecule or family of molecules and which in response brings about regulation of cellular process.#
In the unbound state a receptor is functionally silent

Question 2

Define a ligand

Answer 2

A ligand is any molecule that binds SPECIFICALLY to a receptor site

• If it activates a receptor it is classed as an agonist
• If it binds but doesn’t cause activation it is classed as an antagonist

Question 3

How are receptors classified?

Answer 3

• Classified according to the specific signalling molecule (agonist)
• Sub-classification - based on the affinity of a series of antagonists (or sometimes other agonists)

Question 4

What’s the difference between a receptor and an acceptor?

Answer 4

Receptor - silent at rest, binding stimulates a biological response
Acceptor - Operate in absence of a ligand, Ligand binding alone produces no response

Question 5

In the order of rapidity name the 4 types of signal transduction

Answer 5

“(L)I” - 1) Membrane-bound receptors with integral ion channels - This occurs in the realm of microseconds
“K” - 2) Membrane bound receptors with integral enzyme activity (Kinase linked)
“G” - 3) Membrane bound receptors which couple to effectors through transducing proteins (GPCRs)
“N” - 4) Intracellular receptors - require transcription and translation to occur so are much slower

Question 6

How are nAChR selective to cations?

Answer 6

They have 2 regions of negative charge on either side of the gate that repel anions

Question 7

Give 4 examples of membrane bound receptors with integral ion channels

Answer 7

Receptor - Ion Selectivity

1) nAChR - Gated Na+, K+ and Ca2+ channel
2) Gamma amino butyric acid (GABA) receptor - Gated Chloride (Cl-) Channel
3) Glycine receptors - Gated chloride (Cl-) channel
4) Glutamate receptors (NMDA, Kianate and AMPA) - Gated entry of cations

Question 8

Give some examples of membrane bound receptors with integral enzyme activity

Answer 8

Growth factor receptors - Insulin, Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor (PDGF)
All of these receptors are linked to tyrosine kinase

Question 9

Outline the action of a GPCR protein for a Beta-adrenorecptor

Answer 9

1- Agonist binding releases Gas and Gbg subunits
2- Gas acts as a transducer and stimulates Adenyl cyclase
3- Adenyl Cyclase converts ATP to cyclic AMP

Question 10

Explain the action of intracellular/nuclear receptors

Answer 10

1- Hormone (steroid as is lipid soluble) binds to site and stimulates a conformational change
2- Conformational change releases Inhibitory complex and exposes the DNA binding site. Which allows for transcription and then translation.

Question 11

Name the ligands and receptors involved in the control of heart rate in cardiac pacemaker cells and glycogen synthesis/breakdown in hepatocytes

Answer 11

Cardiac Pacemaker Cells :

• > Noradrenaline - Beta-1-adrenoreceptors - increased heart rate
• > Acetylcholine - M2 muscarinic - slowing heart rate

Hepatocytes

• > Insulin - glycogen synthesis
• > Glucagon - glycogen breakdown