Neurotransmitter Receptors Flashcards
What are G proteins and how do they work ?
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
How do metabotropic receptors work ?
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
How many different GPCRs are there ?
About 1000 different ones
Targets for approximately 30% of medicinal drugs
What 2nd messenger system does norepinephrine use ?
Increase adenyl Cyclase
Increase cAMP
Increase pKA
Increase protein phosphorylation
What 2nd messenger system does glutamate class 1 receptors use ?
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
What 2nd messenger system does glutamate class 2 receptors use ?
Linked to Gi Decrease adenyl Cyclase Decrease cAMP Decrease pKA Decrease protein phosphorylation
What 2nd messenger system does dopamine use ?
Decrease adenyl Cyclase
Decrease cAMP
Decrease pKA
Decrease protein phosphorylation
Where are mGluR1s mostly located and where are mGluR2+3s located ?
1- Post synaptically
2+3- pre synaptically
What is different about glutamate and GABA metabotropic receptors compared to others ?
They are dimers
GABA has to have 2 receptors interacting with each other for it to work
What happens in long term depression in the cerebellum ?
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
How do mGluR2s work at presynaptic neurons ?
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
What are heteroreceptors?
It is an autoreceptors present on the pre synaptic membrane which can inhibit the release of another neurotransmitter
What are GABAb receptors like ?
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
Why is acetylcholine in its own separate group as a neurotransmitter ?
Because there is nothing in the body similar to it
How is acetylcholine made ?
Acetyl CoA + choline
Choline acetyltransferase catalyses it - rate limiting step and is only present in cholinergic neurons
Choline is an essential nutrient, where do we get it from ?
Veg, liver and egg yolks
It is recycled back to synaptic terminal by a choline transporter
What inhibits ChAT ?
Acetylcholine by binding to an allosteric site on it
- acts as a negative feedback loop
How is acetylcholine stored ?
Stored in small clear vesicles
Transported into it by vesicular acetylcholine transporter - VAChT
How is acetylcholine inactivated ?
By acetylcholineesterase
Cleaves it into acetic acid and choline
What does sarin gas do ?
It inhibits the breakdown of acetylcholine so it’s effects are continuously activated
What does hemicolinium do to cholinergic transmission ?
Reduces signalling by blocking the reuptake of choline and therefore preventing reformations of acetylcholine
What does vesamicol do to cholinergic transmission?
Reduces signalling by inhibiting acetylcholine uptake into its vesicles
What does botulinum do to cholinergic transmission ?
Reduces signalling by blocking acetylcholine release by SNARE proteins
What does nicotine do to cholinergic transmission ?
Enhances signalling by acting as an agonist at nicotinic receptors
What does scopolamine do to cholinergic transmission ?
Reduces signalling by acting as a competitive antagonist at mAChRs
What acts as an agonist at muscarinic acetylcholine receptors ?
Amanita muscaria
Where is acetylcholine present in the PNS ?
All motor neurons at neuromuscular junctions
All preganglionic and parasympathetic postganglionic neurons in ANS
Where is acetylcholine present in the CNS ?
It is a major excitatory nt in the CNS but it is not the most important
How are cholinergic neurons identified ?
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
Where are the major cholinergic clusters in the CNS ?
Striatum - interneurons in caudate, putamen and nucleus accuumbens
Basal forebrain - project to cortex and hippocampus
Pontine tegmentum - REM sleep
Where are alpha-3 beta-4 acetylcholine receptors ?
Autonomic ganglia
Where are alpha-7 acetylcholine receptors present ?
Brain- important for attention and cognition
This subunit allows calcium through
Where are alpha-4 beta-2 acetylcholine receptors present ?
Brain
Pre and post synaptically
Where are m1 acetylcholine receptors present ?
Cortex, hippocampus and striatum
Where are m2 acetylcholine receptor?
Very important in heart not a lot of expression in brain
Where are m3 acetylcholine receptors expressed ?
Cortex and hippocampus
Where are m4a acetylcholine receptors expressed ?
Highly in the striatum
In knocked out mice where are the m1 receptors expressed and what is there function ?
Hippocampus, Cortex and striatum
Excitatory causing closure of potassium channels
For cognition memory and learning
In knocked out mice where are the m2receptors expressed and what is there function ?
Throughout brai , hippocampus and Cortex
Reg of body temperature, autoreceptors and cognition
In knocked out mice where are the m3 receptors expressed and what is there function ?
Hypothalamus
Stimulate appetite , memory and learning
In knocked out mice where are the m4 receptors expressed and what is there function ?
Forebrain
Reg dopamine release
In knocked out mice where are the m5 receptors expressed and what is there function ?
Midbrain and low in brain
Reg dopamine release and dilation of cerebral arteries
