L13 Basic Concepts in Pharmacology

Question 1

Which receptor type is used for fast transmission and is directly coupled to an ion channel?

Answer 1

Type 1

a.k.a ionotropic receptors

Question 2

Which receptor type signals via G-protein pathways?

Answer 2

Type 2

a.k.a metabotropic receptors

Question 3

Which receptor type signals via enzyme-linked cell surface receptors?

Answer 3

Type 3

Question 4

Which receptor type is located in specialised regions of DNA, and directly promote gene up-regulation (i.e. activate transcription processes)?

Answer 4

Type 4

Question 5

True or false, Type 1 receptors are associated with fast neurotransmission?

Answer 5

True. Associated with GABA, 5-HT- and ACh

Question 6

Which receptor type is an ionotropic receptor?

Answer 6

Type 1 (ligand-gated)

Question 7

Which receptor type is a metabotropic receptor?

Answer 7

Type 2 (G protein-coupled)

Question 8

Which receptor type is enzyme-linked?

Answer 8

Type 3

Question 9

Which receptor type is intracellular?

Answer 9

Type 4 (DNA-linked)

Question 10

What are the key neurotransmitters associated with ionotropic receptors?

Answer 10

ACh, GABA, 5-HT

Question 11

What kinds of actions are associated with ionotropic receptors?

Answer 11

Breathing and musculoskeletal movements.

Quick actions, autonomic nervous system.

Question 12

A nicotinic receptor is a classic example of a type __1__ receptor.

It consists of __2__, which will only open when __3__.

Once open, this channel enables __4__.

Answer 12

1) 1
2) 5 transmembrane subunits (2x alpha, 1x beta, 1x gamma, 1x delta)
3) 2 ACh molecules bind (one to each alpha subunit)
4) sodium to flow out, causing depolarisation of the cell.

Question 13

Which receptor(s) are involved in intracellular signalling?

(Intracellular signalling is when the binding of a ligand activates an enzyme cascade within the cell, producing a cellular response)

Answer 13

Type 2 (G protein)

Type 3 (enzyme-linked)

(Type 4 receptors are generally stimulated by steroids which are lipid soluble. This means the T4 receptors can be located within the cell as the steroid can cross the plasma membrane)

Question 14

Describe a G protein-coupled receptor

Answer 14

Most consist of a single polypeptide chain of seven transmembrane alpha helices arranged with an extracellular N-terminus and a cytoplasmic carboxy terminus.

(There is a nitrogen on one end that sticks out of the cell and a carbon on the other end that sticks into the cell, with seven loops weaving in and out of the membrane)

Question 15

In a G protein-coupled receptor (type 2), which loop is coupled to a G protein?

Answer 15

The 3rd loop

Question 16

In a G protein-coupled receptor (type 2), where does the ligand bind?

Answer 16

There is a binding site in the alpha helices which are embedded in the membrane.

Question 17

What are the 3 subunits the make up a G protein?

Answer 17

Alpha, beta, and gamma.

Question 18

Which of the G protein subunits are associated with the plasma membrane?

Answer 18

Beta and gamma form a complex that remains bound to the intracellular surface of the plasma membrane,

Question 19

What are the 3 stages of G protein activation?

Answer 19

1) Binding of a ligand to the type 2 receptor - allows a conformational change in the alpha, beta and gamma complex, allowing the alpha to exchange the GDP for a GTP and this causes the alpha to dissociate from the beta and gamma subunits.
2) The alpha coupled to the GTP then associates with specific allosteric target enzyme (such as an adenylate cyclase).
3) The alpha hydrolyses GTP into GDP. This inactivates the enzymatic ability of the alpha subunit whilst allowing the activation of the target enzyme. The inactive alpha subunit then re-associates with the beta and gamma complex

G-protein mechanisms can act as a signal amplifier - a single activated receptor can activate several G proteins.

Question 20

G proteins target a whole range of membrane proteins, most well known include:

• __1__, to produce intracellular cAMP
• __2__, to produce intracellular cGMP
• Phospholipase C/__3__ system
• The regulators of __4__

Answer 20

1) Adenylate cyclase
2) Guanylate cyclase
3) inositol phosphate
4) ion channels

Question 21

Activated adenylate cyclase converts __1__ into __2__.

Answer 21

1) ATP

2) cAMP

Question 22

cAMP functions as a __1__ and is inactivated by __2__, which hydrolyses it into __3__. Drugs such as __4__ can prevent the deactivation of cAMP.

Answer 22

1) second messenger
2) phosphodiesterase
3) 5’-AMP
4) caffeine

Question 23

What is the main target of cAMP?

Answer 23

Inactive protein kinases - it activates them.

Question 24

cAMP plays a part in lots of processes - e.g. increased activity of voltage-sensitive Ca channels in the __1__ and inactivation of myosin light chain kinase in __2__.

Answer 24

1) heart

2) smooth muscle

Question 25

Adrenaline causes liver cells to reduce glycogen synthesis and increase glycolysis. What receptor is associated with this process?

Answer 25

Type 2 (G protein-coupled)

Question 26

Type 2 (G protein-coupled) receptors commonly utilise the adenylate cyclase and cAMP system, but there are others.

In the phosphoinositide system, the G protein activates __1__, which splits __2__ (PIP) into __3__ (DAG) and __4__ (InsP).

Both DAG and InsP act as __5__, each giving different results.

Answer 26

1) phospholipase C
2) phosphoinositide diphosphate
3) diacylglycerol
4) inositol triphosphate
5) second messengers

Question 27

In the phosphoinositide system, DAG results in __1__, while InsP results in __2__.

Answer 27

1) protein kinase C activation

2) Ca2+ release from intracellular stores

Question 28

How does inositol triphosphate cause calcium to be released from intracellular stores?

Answer 28

InsP3 binds to endoplasmic receptors and opens endoplasmic Ca2+ channels. This allows the release of Ca2+ into the cytosol where the Ca2+ can interact with a whole range of targets.

Question 29

Diacylglycerol activates protein kinase C. What events are associated with PKC?

Answer 29

• Muscle contraction
• Inflammatory response
• Increased neurotransmitter release

Question 30

In addition to the cAMP, cGMP, and phosphoinositide systems, how else can G proteins act?

Answer 30

G-proteins can also directly activate ion channels

Interaction of ACh and muscarinic receptors opens potassium channels via a G-protein pathway.

Question 31

Describe the guanylyl cyclase G protein cascade.

Answer 31

Extracellular domain binds the ligand.

On binding ligand, intracellular domain (the guanylyl cyclase) becomes activated and produces cyclic GMP.

Cyclic GMP binds to cyclic GMP-dependent protein kinase (G-kinase)

G-kinase then phosphorylates downstream proteins on either threonine or serine residues.

In this system cGMP acts as a secondary messenger.

Question 32

What is an example of a receptor that uses the guanylyl cyclase cascade?

Answer 32

The receptor for atrial natriuretic peptide.

Question 33

If activation of a type 2 (G protein-coupled) receptor results in contraction, what was most likely activated by the G protein?

Answer 33

Phospholipase C - produces InsP3 (promotes Ca2+ release) or DAG which both activate contractile proteins.

This is the phosphoinositide system.

Question 34

Which G protein pathways can affect ion channels?

Answer 34

All of them. cAMP, cGMP, phospholipase C can all affect ion channels. G proteins can also do this directly, without the need of messengers.

Question 35

What are the four variants of Type 3 (enzyme-linked) receptor?

Answer 35

1) Receptor tyrosine kinases
2) Receptor linked tyrosine kinases
3) Receptor tyrosine phosphatases
4) Receptor serine/threonine kinases.

Question 36

What is the major difference in how a type 2 and type 3 receptor work?

Answer 36

T2 have an intermediary (g-protein) but T3 is direct

Question 37

Where are Type 4 receptors found?

Answer 37

In the nucleus, wrapped around DNA.

Question 38

How do Type 4 receptors respond when a molecule binds?

Answer 38

Typically form target for steroid hormones.

Steroids are lipid soluble, bind to the receptor, the receptor unfolds allowing the receptor to bind to specific DNA sequences (known as hormone responsive elements) and so promote increased RNA polymerase activity and gene transcription.

In this system the DNA receptors are very specific to the hormone.

Question 39

What type of T4 receptor is associated with growth factors and insulin?

Answer 39

Receptor tyrosine kinases

Question 40

What type of T4 receptor is associated with integrins?

Answer 40

Receptor-linked tyrosine kinases

Question 41

What is the function of receptor tyrosine phosphatases?

Answer 41

Hydrolyse target proteins, deactivating them

Question 42

What is the function of receptor serine/threonine kinases?

Answer 42

Phosphorylate proteins

Question 43

Adapter proteins are associated with receptor tyrosine kinases. True or false?

Answer 43

True.