Neurotransmitter Receptors

Question 0

What are G proteins and how do they work ?

Answer 0

Trimeric proteins
Alpha subunit binds GDP and interacts with GPCR
Upon activation the GDP is replaced by GTP causing a conformational change allowing alpha subunit to dissociate from beta-gamma subunit
Now these subunits can inhibit or activate other proteins
G protein diffuses in the plane of the membrane because it is tethered to the membrane by lipids

Question 1

How do metabotropic receptors work ?

Answer 1

Nt binds
G protein is activated
Alpha subunit dissociates from beta-gamma subuni and these can activate enzymes or modulate ion channels allowing ion flow

Question 2

How many different GPCRs are there ?

Answer 2

About 1000 different ones

Targets for approximately 30% of medicinal drugs

Question 3

What 2nd messenger system does norepinephrine use ?

Answer 3

Increase adenyl Cyclase
Increase cAMP
Increase pKA
Increase protein phosphorylation

Question 4

What 2nd messenger system does glutamate class 1 receptors use ?

Answer 4

Linked to Gq
Activates phospholipase C
Increases DAG and IP3
DAG increases pKC and ip3 increases calcium release
Increased protein phosphorylation and activates Calcium binding protein

Question 5

What 2nd messenger system does glutamate class 2 receptors use ?

Answer 5

Linked to Gi
Decrease adenyl Cyclase 
Decrease cAMP 
Decrease pKA 
Decrease protein phosphorylation

Question 6

What 2nd messenger system does dopamine use ?

Answer 6

Decrease adenyl Cyclase
Decrease cAMP
Decrease pKA
Decrease protein phosphorylation

Question 7

Where are mGluR1s mostly located and where are mGluR2+3s located ?

Answer 7

1- Post synaptically

2+3- pre synaptically

Question 8

What is different about glutamate and GABA metabotropic receptors compared to others ?

Answer 8

They are dimers

GABA has to have 2 receptors interacting with each other for it to work

Question 9

What happens in long term depression in the cerebellum ?

Answer 9

mGluRs decrease synaptic activity but they can also increase synaptic activity using NMDA receptors
There is an increase in pKC which phosphorylates many different targets
- thought to phosphorylate AMPA receptors causing them to internalise and reduce their activity

Question 10

How do mGluR2s work at presynaptic neurons ?

Answer 10

Once the glutamate has been released from the neuron it can bind back on itself to the mGluR2 receptors and inhibits adenyl Cyclase which inhibits cAMP and reduces calcium influx so reduces neurotransmitter release

Question 11

What are heteroreceptors?

Answer 11

It is an autoreceptors present on the pre synaptic membrane which can inhibit the release of another neurotransmitter

Question 12

What are GABAb receptors like ?

Answer 12

Metabotropic - inhibitory
Heterodimers- made up of a R1 and R2 subunits
The R1 binds the GABA but it doesn’t work on its own
Inhibit adenyl Cyclase to cause increased activity of potassium channels and also inhibits calcium channels so reduces calcium influx and therefore nt release

Question 13

Why is acetylcholine in its own separate group as a neurotransmitter ?

Answer 13

Because there is nothing in the body similar to it

Question 14

How is acetylcholine made ?

Answer 14

Acetyl CoA + choline

Choline acetyltransferase catalyses it - rate limiting step and is only present in cholinergic neurons

Question 15

Choline is an essential nutrient, where do we get it from ?

Answer 15

Veg, liver and egg yolks

It is recycled back to synaptic terminal by a choline transporter

Question 16

What inhibits ChAT ?

Answer 16

Acetylcholine by binding to an allosteric site on it

- acts as a negative feedback loop

Question 17

How is acetylcholine stored ?

Answer 17

Stored in small clear vesicles

Transported into it by vesicular acetylcholine transporter - VAChT

Question 18

How is acetylcholine inactivated ?

Answer 18

By acetylcholineesterase

Cleaves it into acetic acid and choline

Question 19

What does sarin gas do ?

Answer 19

It inhibits the breakdown of acetylcholine so it’s effects are continuously activated

Question 20

What does hemicolinium do to cholinergic transmission ?

Answer 20

Reduces signalling by blocking the reuptake of choline and therefore preventing reformations of acetylcholine

Question 21

What does vesamicol do to cholinergic transmission?

Answer 21

Reduces signalling by inhibiting acetylcholine uptake into its vesicles

Question 22

What does botulinum do to cholinergic transmission ?

Answer 22

Reduces signalling by blocking acetylcholine release by SNARE proteins

Question 23

What does nicotine do to cholinergic transmission ?

Answer 23

Enhances signalling by acting as an agonist at nicotinic receptors

Question 24

What does scopolamine do to cholinergic transmission ?

Answer 24

Reduces signalling by acting as a competitive antagonist at mAChRs

Question 25

What acts as an agonist at muscarinic acetylcholine receptors ?

Answer 25

Amanita muscaria

Question 26

Where is acetylcholine present in the PNS ?

Answer 26

All motor neurons at neuromuscular junctions

All preganglionic and parasympathetic postganglionic neurons in ANS

Question 27

Where is acetylcholine present in the CNS ?

Answer 27

It is a major excitatory nt in the CNS but it is not the most important

Question 28

How are cholinergic neurons identified ?

Answer 28

Can’t stain acetylcholine so you have stain other markers such as chat and VAChT and acetylcholineesterase
Chat is the most reliable one because acetylcholine can’t be produced without it

Question 29

Where are the major cholinergic clusters in the CNS ?

Answer 29

Striatum - interneurons in caudate, putamen and nucleus accuumbens
Basal forebrain - project to cortex and hippocampus
Pontine tegmentum - REM sleep

Question 30

Where are alpha-3 beta-4 acetylcholine receptors ?

Answer 30

Autonomic ganglia

Question 31

Where are alpha-7 acetylcholine receptors present ?

Answer 31

Brain- important for attention and cognition

This subunit allows calcium through

Question 32

Where are alpha-4 beta-2 acetylcholine receptors present ?

Answer 32

Brain

Pre and post synaptically

Question 33

Where are m1 acetylcholine receptors present ?

Answer 33

Cortex, hippocampus and striatum

Question 34

Where are m2 acetylcholine receptor?

Answer 34

Very important in heart not a lot of expression in brain

Question 35

Where are m3 acetylcholine receptors expressed ?

Answer 35

Cortex and hippocampus

Question 36

Where are m4a acetylcholine receptors expressed ?

Answer 36

Highly in the striatum

Question 37

In knocked out mice where are the m1 receptors expressed and what is there function ?

Answer 37

Hippocampus, Cortex and striatum
Excitatory causing closure of potassium channels
For cognition memory and learning

Question 38

In knocked out mice where are the m2receptors expressed and what is there function ?

Answer 38

Throughout brai , hippocampus and Cortex

Reg of body temperature, autoreceptors and cognition

Question 39

In knocked out mice where are the m3 receptors expressed and what is there function ?

Answer 39

Hypothalamus

Stimulate appetite , memory and learning

Question 40

In knocked out mice where are the m4 receptors expressed and what is there function ?

Answer 40

Forebrain

Reg dopamine release

Question 41

In knocked out mice where are the m5 receptors expressed and what is there function ?

Answer 41

Midbrain and low in brain

Reg dopamine release and dilation of cerebral arteries