Receptor Basics

Question 1

What is constitutive activity?

Answer 1

When a receptor is always activated, even when no ligand is bound

Question 2

What is affinity?

Answer 2

Ease with which a ligand binds to it’s receptor

Measured in terms of Kd (conc of drug needed to occupy 50% of receptors)

Question 3

What is efficacy?

Answer 3

Ability of ligand-receptor complex to elicit desired response. Measured in terms of Emax

Question 4

What is potency?

Answer 4

The amount of drug required to elicit a response of a given intensity. Product of affinity and efficacy. Measured in terms of EC50

Question 5

What is an allosteric modulator?

Answer 5

Impacts receptor function by binding at allosteric site away from active site
May cause conformational change
Can have efficacy modulators and affinity modulators

Question 6

What is a neuromodulator?

Answer 6

Biochemical that modulates ability of neurons to respond to neurotransmitters
Can diffuse long distances through neural tissue, to modulates regions of the brain
Chemicals can act as both neurotransmitters and neuromodulators depending on receptor
e.g. D-serine, Glutamate

Question 7

How do neuromodulators signal?

Answer 7

Through GPCR receptors

Question 8

Examples of neuromodulators

Answer 8

D-serine
Glutamate
Dopamine
Serotonin
Ach

Question 9

What are the amino acid neurotransmitters (and are they excitatory or inhibitory?)

Answer 9

Glutamate (+)
GABA (-)
Aspartate (+)
Glycine (+ or - depending on receptor)

Question 10

What are the biogenic amine neurotransmitters?

Answer 10

Ach
Histamine
Monogenic amine: 5-HT
Catecholamines: NA, A, Dopamine

Question 11

How does NO act as a neurotransmitter?

Answer 11

NO activates cyclicGMP and the MAPK cascade
These pathways lead to increased calcium concentration in the cell
Which increases vesicle exocytosis

Question 12

What are gliotransmitters?

Answer 12

Molecules released by glial cells - primarily from astrocytes
They are involved in signalling between glial cells and neurons
Modulate excitability by changing intracellular calcium concentrations

Question 13

Examples of gliotransmitters

Answer 13

Eicosanoids
Cytokines
Neuropeptides
D-Serine 
Adenosine
Glutamate 
ATP

Question 14

How many subunits do ionotropic receptors have?

Answer 14

NMDA, AMPA and Kainate have 4

GABAa has 5

Question 15

What is the most abundant neurotransmitter?

Answer 15

Glutamate

Question 16

Which glutamate/GABA receptors can be allosterically modulated?

Answer 16

NMDA
GABA-a
GABA-b

Question 17

Examples of ligands for kinase receptors

Answer 17

Insulin, IGF-1, IGF-2, Prolactin, Lectin, Cytokines

Question 18

Response times of each receptor type

Answer 18

Ionotropic - milliseconds
GPCR - seconds/minutes
Kinase linked - minutes/hours
Nuclear - hours/days

Question 19

How are kinase receptors modulated?

Answer 19

By cytokines

Question 20

How can nuclear receptors affect neurotransmission?

Answer 20

By upregulating expression of genes for small molecule neurotransmitters

Question 21

What is receptor desensitisation?

Answer 21

Following chronic exposure, when an agonist binds it produces a reduced signalling response

Question 22

What are the 3 mechanisms that contribute towards receptor desensitisation?

Answer 22

1. Receptor internalisation into the membrane
2. Reduced expression/synthesis of the receptor
3. Homologous desensitisation

Question 23

What is homologous desensitisation?

Answer 23

Uncoupling of the intracellular response from the ligand-receptor complex

Question 24

What is tachyphylaxis?

Answer 24

Sudden dramatic decrease in response to a drug, shortly after administration
Usually caused by receptor internalisation

Question 25

What is tolerance?

Answer 25

Reduced response to a drug following chronic use

Requires an increased dose to produce the same effects

Question 26

How does receptor desensitisation happen to GPCRs?

Answer 26

Mediated by arrestin proteins
The GPCR is phosphorylated by a GPCR specific kinase (GRK)
Recruitment of the beta-arrestin complex Marks the receptor for internalisation, and re-directs the signalling pathway (homologous desensitisation)

Question 27

Give an example of a GABA-b agonist

Answer 27

R-Baclofen

Question 28

Give an example of a GABA-b antagonist

Answer 28

CGP55845

Question 29

Give and example of an AMPA antagonist

Answer 29

NBQX