Neurotransmitters Flashcards
Criteria for neurotransmitters
- Present in the pre-synaptic terminals
- Released in response to stimulation
- Able to interact with postsynaptic receptors
- Rapidly removed from the synapse
What do neurotransmitters need mechanisms for?
- Synthesis and/or storage
- Release
- Receptors
- Transmitter removal
Types of neurotransmitters?
- Acetylcholine
- Amino acids eg. GABA/glycine
- Biogenic amines e.g. dopamine/adrenaline
- Neuropeptides e.g. enkephalin
Characteristics of amino acid and amine NTs
- Small molecules
- Stored and released from synaptic vesicles
- Many activate both ligand-gated channel receptors and G-coupled receptors
Characteristics of peptide NTs
- Large molecules
- Stored in secretory granules
- Only activate G coupled receptors
What is Dale’s principle?
A single neuron has only one neurotransmitter
Why is Dale’s principle violated?
Many peptide-containing neurons have both peptide transmitter and an amino acid or amine NT
Which amino acids are abundant in all cells?
Glutamate and glycine
Where is synthesis localised to for ACh, GABA and amines?
Axon terminal by specific enzymes
What is the most common excitatory transmitter in the CNS?
Glutamate
Which receptors does glutamate bind to?
AMPA and NDMA
What does glutamate binding to AMPA receptors trigger?
Na+ and K+ currents producing an EPSP
How are NMDA receptors activated?
Indirectly by another transmitter other than glutamate as they have a voltage-dependent Mg+ block
What is the most common inhibitory transmitter in the brain?
GABA
What does too much GABA action cause?
A coma
What does too little GABA action cause?
Seizures
What channels does GABA use?
GABA-gated chloride channels (produces IPSP)
Where is GABA found?
Primarily in the brain - especially in the cortex and striatum
What is disinhibition?
Inhibiting inhibition
How are peptides synthesised?
Formed int he rough ER and packaged into secretory granules
What are the main types of opiate receptors?
Mu (µ), kappa (κ) and sigma (σ)
Opiate effect on spinal cord
Block pain signal
Opiate effect on periaqueductal grey
Regulates sensation of pain
Opiate effect on amygdala
Regulates emotional aspect
Opiate effect on frontal cortex
Cognitive aspects
Opiate effect on brain stem (medulla)
Depress respiration and cough reflex (may induce vomiting)
What type of receptors are opiate receptors?
G-coupled
Therapeutic uses of opiates
Analgesia - reduces perception of and emotional response to pain
Intestinal disorders - reduces diarrhoea and decreases dehydration
Antitussive - cough suppressant (codeine)
Problems with opiates
- Tolerance and dependence develop
- Analgesic and euphoric effects are linked
- Analgesic and dependence liability are linked
- Relieve dull visceral pain better than sharp pain
Diffuse modulatory systems of the brain
- Cause effects over large areas of the brain
- Core nuclei in central part of the brain (often brain stem)
- Neurons may contact large numbers of postsynaptic neurons
- ‘Hosepipe effect’
Which transmitters are involved in the diffuse modulatory systems?
- Catecholamines (dopamine, noradrenaline, adrenaline)
- Serotonin
- ACh
Which places is ACh distributed?
- Autonomic nerves
- Neuromuscular junction
- Basal forebrain
- Hippocampus
What is ACh associated with?
- Memory
- Co-ordination
- Sleep cycle
- Mood
- Aggression
Which neurotransmitter is lost in Alzheimer’s?
ACh
What prevents the release of ACh?
Botulinum toxin (used in botox)
What are some acetylcholinesterase (AChE) inhibitors?
- Nerve gas
- Insecticides
- Alzheimer’s treatments
What blocks nicotinic ACh receptors?
- Curare
- a-bungarotoxin
What blocks muscarinic ACh receptors?
Atropine
What are catecholamine systems associated with?
Movement, mood, attention and visceral function
What is L-dopa synthesised from?
Tyrosine + Tyrosine hydroxylase (TH)
What is dopamine synthesised from?
L-dopa + dopa decarboxylase
What is noradrenaline synthesised from?
Dopamine + dopamine b-hydroxylase (DBH)
What is adrenaline synthesised from?
Noradrenaline + phentolamine N-methyltransferase (PNMT)
How many people over 70 does Parkinson’s affect?
1 in 200
Symptoms of Parkinson’s
- Tremor
- Rigidity
- Akinesia (loss of power of movement)
- Postural changes - stoop and shuffling gait
- Monotonus slurred speech
- No sensory loss
- Normal cognitive function (at the start)
Pathology of Parkinson’s
Diminished substantia nigra seen
What do striatum do?
Inhibit motor function
What goes wrong in Parkinson’s disease?
- Dopamine usually inhibits cells of the striatum via D2 receptors (decreases their inhibitory action)
- This inhibition is lost in Parkinson’s and so inhibition is increased, therefore motor function is inhibited
Treatments for Parkinson’s
- L-dopa (increases dopamine)
- Cocaine blocks re-uptake of DA
- Selegiline
Problems with L-dopa treatment
- Drug becomes ineffective in long term
- Chronic L-dopa syndrome - dopa-induced dyskinesias fluctuating with sudden and severe immobility (on-off syndrome)
What is a problem with antipsychotic medication acting on DA receptors?
May induce Parkinson’s
Where does the noradrenaline system arise from?
The locus coeruleus
What is the noradrenaline system associated with?
Attention, arousal, learning and memory, anxiety
How are catecholamines broken down and removed?
- Most reuptake into the presynaptic terminal
- Metabolised by catechol-O-methyltransferase (COMT) mainly in the cytoplasm
- Monoamine oxidase (MAO) on outer mitochondrial membrane
What does MAO-A metabolise?
Mainly NA and 5-HT
What does MAO-B metabolise?
Mainly dopamine
MAO-inhibitors have been used to treat…?
Depression - increases NA + 5-HT
Parkinson’s - increases dopamine
What is 5-HT also known as?
Serotonin
Functions of serotonin?
- Consciousness/arousal
- Circadian rhythms
- Mood
- Aggression
Treatment of depression
- Tricyclic antidepressants - block serotonin and NA uptake
- SSRIs - e.g. Prozac
- MAO-A inhibitors
