Neurotransmitters and receptors Flashcards
How would you classify a neurotransmitter?
The chemical needs to fall into all three criteria:
Be synthesised and stored (generally in synaptic vesicles) in presynaptic neuron.
Be released by presynaptic axon terminal.
Produce responses in postsynaptic cell (fuction at the synapse).
What is an agonist?
Agents (neurotransmitters; drugs) which bind to and activate receptors are called agonists.
What is an inverse agonist?
Agents that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist are called Inverse agonists.
What is an antagonist?
Agents which block receptors and prevent agonists/inverse agonists from binding to their respective receptors are called antagonists.
What are ionotropic receptors?
Their activation results in the passage of ions and mediate fast synaptic neurotransmission.
These receptors are proteins embedded in the cell membrane which form pores or channels for passing different ions between the inside & the outside of the neuron.
When the agonist binds to these receptors, the channels open and allow the movement of these ions into the neuron.
This movement of charge creates electrical currents
& changes the electrical potential of the inside of
the cell which changes its excitability.
Explain what happens during synaptic transmission:
What are metabotropic receptors?
Their activation leads to intracellular metabolic pathway signalling and they mediate slow synaptic neurotransmission.
Belong to the family of G-protein coupled receptors.
These receptors are proteins embedded in the cell
membrane but don’t form pores or channels for
passing different ions.
Instead, they are coupled to intracellular regulatory proteins/enzymes.
The binding of the agonist to these receptors initiates an intracellular biochemical cascade which generally
results in the increase or decrease of other intracellular
proteins or calcium levels which then results in neuronal excitation.
Requires a number of biochemical pathways, so the effects take much longer.
What is glutamate?
Main excitatory CNS neurotransmitter.
Expressed widely by principals neurons of various part of the brain.
Fast acting neurotransmitter causing excitation of the postsynaptic neurons.
Acts on both ionotropic and metabotropic receptors.
NMDA receptor is one of the main targets.
Why is glutamate important in brain function?
Glutamate important for different forms of learning memory:
Learning and memory occurs through strengthening of synapses which is called long term potentiation (LTP).
LTP is mediated by glutamate.
Enhance cognition.
Can lead to excessive excitability of neurons:
Seizures and epilepsy.
Hypoxia in stroke, excessive glutamate, excitotoxicity in stroke.
NMDA antagonist as drugs of abuse (Ketamine; PCP).
NMDA impairment implicated in schizophrenia.
Most current drugs are still in experimental stages.
What is gamma-aminobutyric acid (GABA)?
Main inhibitory CNS neurotransmitter.
Widely expressed by interneurons throughout the brain.
Decreases the activity of neurons leading to less chance of the neuron firing an action potential.
Acts on both ionotropic and metabotropic receptors.
Why is GABA important in brain function?
Pathogenesis of anxiety:
Benzodiazepines (eg. diazepam) relieve anxiety by facilitating GABAa transmission.
Muscle tone and Epilepsy:
GABAb agonists inhibit release of excitatory transmitters.
Baclofen used to treat spasticity.
Benzodiazepines used to treat status epilepticus (eg. diazepam).
Movement control:
GABA is a major transmitter in the basal ganglia.
Huntington’s disease:
Due to loss of GABA-containing long projection neurones leading to uncontrolled movement and cognitive deficit.
What is acetylcholine?
Acetylcholine is a quaternary amine.
Members include:
Noradrenaline
Serotonin
Dopamine
Differ from Glutamate and GABA in that they are expressed only in select populations of neurons in specific brain regions, whereas GLUT/GABA are expressed throughout the brain.
Allows for functional specialisation of certain brain regions or centres.
The collection of neurons which express a common chemical is called a nucleus, e.g. one gets groups of neurons which commonly express dopamine (DA). We call them dopaminergic nuclei.
What is the role of dopamine in brain function?
Motor coordination
Motivation
Reward seeking
Cognition
Nausea & vomiting
Hormonal
Cause excitation or inhibition depending upon the G-proteins they are coupled to.
How do ligands and drugs work at dopaminergic synapses?
What is the role of noradrenaline in brain function?
Arousal (how awake you are).
Memory & cognition.
Stress response.
Cause excitation or inhibition depending upon the G-proteins they are coupled to and their location (pre or postsynaptic).
How do ligands and drugs work at acetylcholine synapses?
How do ligands and drugs work at noradrenaline synapses?
How do ligands and drugs work at 5HT synapses?
