CAL Flashcards
What are the peptide neurotransmitters of the CNS?
Substance P
Cholecystokinin
Enkephalins
Somatostain
What are the non-peptide neurotransmitters of the CNS?
Noradrenaline Acetylcholine GABA Glutamate Dopamine 5-HT
Give the sequence for the steps involved in neurotransmitter transmission (LONG)
Neurotransmitter synthesis: peptide synthesis occurs in the nucleus and non-peptide synthesis occurs in the pre-cursor terminals - active uptake of the neurotransmitters into the pre-synaptic neurone
The neurotransmitters are then stored within vesicles
Neurotransmitters are released when stimulated by an action potential and they invade the terminal - depolarisation of the neurone occurs
Neurotransmitter presence stimulates the opening of the voltage gated Ca2+ channels and Ca2+ ions enter the terminal
There is an increase in the intracellular concentration of Ca2+ - causes the storage neurotransmitter vesicles to move towards and fuse with the terminal membrane and they are released across the synapse
Neurotransmitters diffuse across the synaptic cleft and bind to receptors on the post synaptic membrane - the action potential is transmitted
Termination occurs via reuptake of the non-peptide neurotransmitters at the pre-synaptic terminal, metabolic degradation and diffusion of neurotransmitters away from the synapse
How long is the typical synaptic delay between the depolarisation of the pre-synaptic terminal to the onset of the post-synaptic response?
0.5 seconds
What are the different post synaptic receptor types?
Ligand gated ion channels is the major one - entrance for amino acids - two neurotransmitters generally must bind for this channel to open
G-protein coupled receptors - single polypeptide chain spanning the membrane seven times - has long lasting effects and works via the displacement of GDP by GTP which then activate the effector protein
What different factors can result in the depolarisation of a membrane?
Excitatory neurotransmitters binding to and activating pre-synaptic fibres
Influx of Ca2+
Closing of K+ channels
Efflux of Cl-
What different factors can result in inhibitory post synaptic potentials (IPSPs)?
Inhibitory neurotransmitter release
Opening of K+ channels
How is dopamine synthesised?
Amino acid tyrosine uptake into nerve terminal
Enzyme tyrosine carboxylase converts tyrosine to DOPA
Enzyme DOPA decarboxylase converts DOPA to dopamine
NB. L-dopa is formed from L-tyrosine
How and where is dopamine stored and what is this dependant on?
Taken up via an active process requiring ATP and is stored in presynaptic vesicles
Storage is dependant on the vesicular monoamine transporter 2 (VMAT2)
Name some neurological conditions in which dopaminergic pathways are involved
Parkinson's disease Schizophrenia Huntington's disease Addiction Chronic pain syndromes
How does dopamine release from the synapse occur?
This is initiated by depolarisation at the presynaptic terminal via an action potential - influx of Na+ carried by the action potential causes the opening of voltage gated N-type calcium channels at the synaptic membrane into the synaptic cleft
Which receptors can dopamine bind to and activate?
Can diffuse across synaptic cleft and bind to and activate post synaptic dopamine receptors D1 or D2
OR can bind to and activate pre-synaptic autoreceptors D2
How is dopamine inactivated once it has bound to its receptors?
Some of the dopamine leaves the synaptic cleft via diffusion
Some is taken up back into the nerve terminal via active transport - this is known as ‘reuptake’ and involves a protein channel
Following reuptake, the dopamine is then either stored into vesicles ready for release again
OR degraded to homovanilic acid (HVA) via COMT and to DOPAC via MAO
What is homovanillic acid (HVA)?
This is a major metabolite of dopamine and its levels are used to determine the dopamine turnover
What type of receptors are dopamine receptors and what are the different types?
They are g-protein coupled receptors and are classified into the D1 and D2 receptor type families
D1 family: D1 and D5
D2 family: D2, D3 and D4
What are the actions of the D1 receptor family and where is each type found?
These receptors are post synaptic and activate adenylate cyclase
D1:
Found mainly in caudate-putamen, nucleus accumbens and olfactory bulbs
Lesser amounts in the cerebral cortex, limbic system and hypothalamus
D5:
Found in much lower concentrations than D1
Found highest in the hippocampus and the hypothalamus (limbic regions)
What are the actions of the D2 receptor family and where is each type found?
These have the following effects: Inhibit adenylate cyclase Activate K+ channels Decrease Ca2+ conduction Potentiate ATP-mediated arachidonic acid release
D2:
Found in the caudate-putamen, nucleus accumbens and olfactory bulb
Mainly post-synaptic but can be presynaptic
D3:
Less abundant
Found mainly in limbic areas
Mediate control of emotional and cognitive functions
D4:
Found in frontal cortex, midbrain, amygdala and medulla
