1. Receptors

Question 1

Receptors

Ligand

Answer 1

Receptors = Are proteins, usually integral to the cell membrane, with selective ligand-binding sites.

Ligand is any substance able to bind to a receptor and bring about biological change within the cell.

A ligand may be capable of binding to more
than one receptor and exerting different effects at each different one.

Question 2

What governs drug–receptor

interactions?

Answer 2

The law of mass action governs drug–receptor interactions and so the rate of interaction is proportional to the concentration of drug and receptor.
It is a specific, dose-dependent and saturatable interaction.

Question 3

Table in book with receptor classes

Answer 3

page 2

Question 4

What are the main mechanisms

of receptor action?

Answer 4

1. Altered ion permeability:
   Acetylcholine (ACh) binds to the two α subunits of the pentameric nicotinic acetylcholine receptor (nAChR), causing a conformational change, which opens a central pore allowing an influx of Na+ ions,
   leading to cell depolarisation.
2. > Intermediate (secondary) messengers:
   There are several types of secondary messengers including
   cyclic adenosine monophosphate (cAMP),
   cyclic guanosine monophosphate (cGMP),
   inositol triphosphate (IP3),
   diacylglycerol (DAG) and
   calcium ions (Ca2+).

cAMP is activated by Gs proteins (e.g. via stimulation of β
adrenoceptors and glucagon receptors).

3. > Regulation of gene transcription:
   • These receptors are located intracellularly and are targeted by lipidsoluble ligands, typically hormones (e.g. thyroxine and steroids), that
   can diffuse easily into the cell.

Question 5

What is the structure of the G-protein-coupled receptor

(GPCR)?

Answer 5

1. GPCR consists of seven α helices, which span the cell membrane forming an extracellular site (where the ligand binds) and an intracellular site (where the G protein attaches).
2. Each GPCR can be associated with up to a hundred G proteins, which promotes signal amplification.

Question 6

What are G proteins? >

Answer 6

G proteins (or GTP-binding proteins) are regulatory proteins, which couple the activation of a surface receptor to the activation of an intracellular enzyme (e.g. adenylate cyclase) so that a secondary messenger can be produced (e.g. cAMP), allowing signal
transduction and amplification to occur.
> They are heterotrimeric proteins (i.e. they consist of α, β and γ subunits,
which join together to form a trimer).

Question 7

Which different types of G proteins are there?

Answer 7

> Gs proteins stimulate adenylate cyclase, causing a rise in cAMP (e.g. β adrenoceptors and glucagon receptor).
Gq proteins stimulate phospholipase C, causing a rise in IP3 and DAG (e.g. α1 adrenoceptor and muscarinic acetylcholine receptor (mAChR)).
Gi proteins inhibit adenylate cyclase, causing a fall in cAMP (e.g. α2 adrenoceptors and opioid receptors)

Question 8

What happens when a GPCR is

activated?

Answer 8

> When a ligand binds to the extracellular site of a GPCR,

it causes a GTP molecule to bind to the intracellular

α subunit of the G-protein trimer.

> This causes a conformational change
within the trimer, resulting in its

separation from the receptor and

dissociation into a βγ and an α-GTP complex.

> The α-GTP complex then goes on to

activate (or inhibit) the various enzymes systems

(e.g. adenylate cyclase, guanylate cyclase and phospholipase C)

resulting in the production
of the secondary messengers.

> The α subunit has intrinsic
GTPase activity and
so it converts the GTP into GDP.

> Once the α subunit is bound only to GDP, it rejoins the βγ units to return to its resting state. The reformed G-protein trimer reattaches to the intracellular portion of the receptor and the receptor system is ready to
be stimulated once again