Neurotransmitters & Their Receptors Flashcards
What is GABA?
The main inhibitory neurotransmitter in the brain
It is synthesised from Glutamate by glutamic acid decarboxylase
Loaded into synaptic vesicles by vesicular inhibitory amino acid transporter
What are the two classes of receptors for GABA?
Ionotropic & Metabotropic
GABAa- ionotropic class- 5 different subunits assembled, two alpha, two beeta and a gamma/delta/pi and these assemble to form a chloride channel
GABAb-metabotropic class- g protein coupled receptor, so GABA binds on the outside of the cell, its got transmembrane helices and then the intercellular part interacts with these g proteins and then this activates signalling pathways which acts on channels
GABAa - causes hyperpolarisation through efflux of chloride, going to make the membrane more negative on the inside
GABAb- channels work in a different way, so by causing an efflux of potassium, so this is hyperpolarising and making the cell more negative on the inside
What drugs block the activity of GABAa?
Bicuculline & Flumazenil
What drugs activate GABAb receptors?
Baclofen - for spasticity (MND, MS treatments)
What are GABA reuptake inhibitors and what condition do they help?
Tiagabine/Gabitril
Used for focal seizures
What GABA agonist activates GABA receptors and what conditions do they help?
Gabapentin
Used for seizures and neuropathic pain
What is Glycine?
The other main inhibitory neurotransmitter
It is synthesied by serine hydroxyl-methyltransferase
Uses VIAAT to be loaded into the synaptic vesicles
Cleared by GlyT
What mutation causes hyperekplexia (low tone, exaggerated startle)?
Gly2 mutations
What is the result of the poison strychnine acting on Glycine?
Causes excitation and induces seizures
What are purines?
E.g. ATP which is an excitatory neurotransmitter in the CNS and PNS
ATP is rapidly catabolised to adenosine
BUT adenosine doesnt meet the full NT criteria
Drugs targetting purinergic receptors treat what?
Treatment of chronic pain
Inhibitors of the receptor P2Y12 are anti-platelet agents used for clotting
What is dopamine invovled in and what diseases are these linked to?
Movement –> linked to PD
Motivation reward & enforcement –> linked to drug addiction
Cognition & emotion
Schizophrenia
Dopaminergic projections
What is the nigro-striatum projection?
Its linked to movement
Cell bodies are localised in the substantia nigra in the midbrain and project to the striatum and in particular the putamen
Dopaminergic projections
What is the Mesolimbic projection?
It linked to reward and addiction
From the midbrain part of the limbic system, so from the ventral midbrain or ventral tegmentum area to the nucleus accumbens
Dopaminergic projections
What is the Mesocortical projection?
Its linked to cognition, emotion and motivation
Going from the midbrain but then projecting extensively throughout the cortex so in limbic structures like the cingulate gyrus and also extensively throughout the frontal cortex too
Which two enzymes break dopamine down?
MAO (monoamine oxidase) and COMPT (catechol-O-methyltransferase)
How are MAO and COMPT used in PD?
MAO-B inhibitors are given to PD patients before they are put on L-Dopa and can also be used in combination with L-Dopa later in the disease
COMPT inhibitors are my typically used in combination with L-Dopa to manage the symptoms of PD
What are the 2 classes of dopamine receptors?
(all dopamine receptors are metabotropic)
D1-like - D1 and D5 receptors
D2-like- D2, D3 and D4 receptors
D1-like couple via Gs which is a stimulatory G protein
D2-like couple via Gi whihc is an inhibitory G protein
What is the main place in whihc neuroadrenaline neurons are located?
In the locus coeruleus in the midbrain
What is the main place in which adrenaline is located in the brain?
Cell bodies are localised in the brain stem
What do beta blockers act on?
They act on beta adrenergic receptors and can be used to treat cardiac arrhythmias and migraines as well
Can antihistamines cross the BBB?
Yes
e.g. Promethazine crosses the BBB and targetes H1 receptors making it a powerful sedative
What drugs target the serotonin system?
Many antidepressants and anxiolytics act by increasing the serotonin system
SSRI act on serotonin transporters–> by blocking these we reduce the uptake of serotonin from nerve terminals and increase serotonin leveles and serotonergic transmission
But too much prozac e.g. in excess serotonergic agonism a.k.a. serotonin syndrome, can be bad, causing mild shivering & diarrhea to severe rigidity, fever & seizures
Loss of serotonergic neurons is an additional feature of PD
What are some agonists/antagonists targetting 5-HT (serotonin) and what do they treat?
Sumatriptan (agonist) –> treats migraines
Ondansetron(antagonist) –> treats nausea/vomitting from chemotherapy
Fenfluramine (antagonist) –> suppresses appetite
What are some of the functions of peptide neurotransmitters?
Pain –> substance P & opioid peptides
Stress responses –> CRH/CRF
Food intake –> NPY, melanocortins
Pituitary peptides –> vasopressin, oxytocin
