Dopamine neurotransmission Flashcards
1
Q
Describe the structure of dopamine.
A
- Catechol ring
- Hydroxyl groups
- Amine group
2
Q
How is dopamine synthesised?(words)
A
- Synth by tyrosine (from diet) in the two steps
- Rate limiting step=tyrosine hydroxylase (TH) enzyme
- Negative feedback loop-dopamine inhibits own prod.
3
Q
How is dopamine synth? (diag)
A
4
Q
What is DAT?
A
- Dopamine transporter protein
- Uses ion gradient created by Na+/K+
- ATPase-main deactivation method-DA reuptake into nerve terminal to end synaptic activity-DA isrecycled
- DAT binding site for cocaine-inhibits reuptake so inc synaptic DA
- Cytoplasmic DA taken up into vesicles by VMAT-2 (Vesicular monoamine transporter protein)
*
5
Q
What happens if you knockout DAT gene?
A
- Elevates synaptic leve of DA in all brain regions with DA terminals
- Enhancing DA neurotransmission in the striatum casuing hyperactivity.
6
Q
What is 6-hydroxydopamine?
A
- A selective neurotoxin
- Similar to dopamine so taken up by DAT
- Auto-oxidised and creates H2O2
- This causes mitochondrial dysfunction via:
- Oxidative stress, casuing cytochrome C leading to death of dopamine and noradrenaline neurones.
7
Q
How is dopamine motabolised?
A
- 2 pathways that lead to the same end result
1.Monoamine oxidase(MAO) on inner mitochondrial membrane
2.COMT in cytosol but also membrane bound.
3.They act in either order to produce common metabolite HVA - SO Can go MAO->product->COMT->HVA or Vice Versa.
- (COMT/MAO imp for DA inactivation in brain areas like frontal cortex where little DAT)
8
Q
What can HVA be used for?
A
- Brain accumulation of HVA used asindex of DA neuronal activity
9
Q
What determines the type of neuron?
A
- A neuron is dopaminergic, noradrenergic, or adrenergic depends on presence and activity of enzymes present.
10
Q
What makes dopaminergic neurones different from nora and adrenergic?
A
- Lacks two enzymes
- Doesn’t have dopamine B-hydroxylase
- Doesn’t have PNMT
11
Q
What makes noradrenergic neurones different from dopamine and adrenergic?
A
- It has dopamine B-hydroxylase that dopaminergic doesnt.
- Lacks PNMT adrenergic has
12
Q
What makes adrenergic neurones different from dopaminergic and noradrenergic?
A
- Has all enzymes
13
Q
What are the receptors for dopamine?
A
- 5 subtypes: G protein coupled receptors
- D1-D5
- D1+D5 are both post-synaptic and D1 like, coupled to cAMP signalling INC
- D2+D3+D4 are D2 like, coupled to cAMP sig dec
14
Q
List the 5 sub types and where they are found?
A
- D1–Post-synaptic
- D2–Pre and post synaptic:striatum levels high
- D3–Post syn:Nucleus acc-VTA pathwya, Pre syn in cortex?
- D4–Pre and Post synp:Frontal cortex, amygdala, hippocampus
- D5–Post syn
(Few drugs bind specifically to each type-each rec has dif dist, affinities, and func.)
15
Q
How many dopamine pathways are there and what are they?
A
- 4
1. Nigrostriatal Pathway–Substantia nigra innervates the basal ganglia:controls planning and execution of vol movt
2. Mesolimbic pathway–Midbrain ventral tegmental area neurones innervate nucleus accu, part of limbic syst cont emotion, pleasure reward and goal-directed behaviour.
3. Mesocortical Pathway–Dopamine neurones in ventral tegmental area (VTA). Innervate the frontal cortex and neuronal activity is associated with emotion and motivation.
4. Tuberinfundibular pathway–In the aruate nucleus of the hypothalamus innervate the median eminence in the anterior pituitary gland (DA release inhibits prolactin secretion; inv in maternal behaviour
