5. MONOAMINES Flashcards
1
Q
What are 4 monoamine systems & their neuronal cell bodies?
A
- Noradrenergic - locus coerculus
- Dopaminergic - VTA (ventral tegmental area) & Substantia Nigra
- Serotonin - Raphe nuclei
- Acetlylcholine - Basal forebrain, brain stem complexes
2
Q
What is the diffuse modulatory system?
A
- The monoamine systems have a diffuse-modulatory effect
- This means that the effect is modulatory rather than direct inhibition or excitation like GABA & Glycine
- They have a slower, widespread effect compared to point to point communication . Neurotransmitters are released & then diffuse out to their receptors
3
Q
What is the noradrenergic system?
A
- The noradrenergic system uses the neurotransmitter Noradrenaline or norepinephrine
4
Q
What are the functions of noradrenaline?
A
- Mood
- Arousal
- Wakefulness
- Exploration
- Blood pressure regulation
5
Q
What’s the neuronal cell body for the noradrenergic system & it’s projections?
A
- The neuronal cell body is located in the LOCUS COERCULUS
- It projects to cortical regions, hypothalamus, amygdala, spinal cord, cerebellum etc.
6
Q
Describe the synthesis & storage of noradrenaline
A
- Noradrenaline is synthesised from dopamine
- Tyrosine -> L-DOPA -> Dopamine -> Noradrenaline
- DOPAMINE BETA HYDROXYLASE is the enzyme involved in converting Dopamine to Noradrenaline
- NA is stored in vesicles by the transporter VMAT
7
Q
Describe the re-uptake & degradation of Noradrenaline
A
- Re-uptake by of NA NERT/NET (Noradrenaline re-uptake transporters) into pre-synaptic neurone
- Can be metabolised by MONOAMINE OXIDASE which terminates NA activity
- Can also be degraded by Catechol-O-methyltransferase
8
Q
Where can noradrenaline receptors be found & what are the three types?
A
- Noradrenaline receptors are G-protein coupled receptors
- They can be located post-synaptically & pre-synaptically
1. Alpha 1
2. Alpha 2
3. Beta
9
Q
What are the effects of the alpha 1 NA receptor?
A
- Alpha 1 receptors = PLC
- Converts PIP2 -> DAG + IP3
- Increase in intracellular Ca2+ = smooth muscle contraction
10
Q
What are the effects of the alpha 2 NA receptor?
A
- Alpha 2 can act as an autoreceptor, meaning it can have an inhibitory effect
- Alpha 2 is negatively coupled to Adenylate cyclase = decreased cAMP & Ca2+. Inhibits NA release
11
Q
What are the effects of the beta NA receptor?
A
- The beta receptor is positively linked to adenylate cyclase = increased cAMP & Ca2+
- Causes smooth muscle relaxation & contraction of cardiac muscle
12
Q
What do reserpine & amphetamine do?
A
- Both reserpine & amphetamine are drugs affecting the noradrenergic system
- Reserpine - blocks NA re-uptake, depletes NA stores causing an accumulation of NA
- Amphetamine - enters vesicles & displaces NA, leading to NA accumulation
13
Q
What is the dopaminergic system & it’s neuronal body ?
A
- The dopaminergic system uses the neurotransmitter dopamine which is a monoamine & catecholamine
- The cell body of dopaminergic neurones is located in the VTA (Ventral Tegmental area) & the Substantia Nigra which project to various areas of the brain forming 4 pathways
14
Q
What are the four pathways of the dopaminergic system?
A
- NIGRO-STRIATAL
- MESOLIMBIC
- MESOCORTICAL
- TUBERO-HYPOPHYSEAL PATHWAY
15
Q
What is the nigrostriatal pathway of the dopaminergic system?
A
- Projects from substantia nigra to the striatum of the basal ganglia
- Involved in motor control
- Disorders e.g Parkinsons - degradation of nigro striatal neurones
16
Q
What is the mesolimbic pathway of the dopaminergic system?
A
- Mesolimbic pathway projects from the ventral tegmental area to the nucleus accumbens of the basal ganglia
- Involved in pleasure & reward
- Hyperactivity of mesolimbic pathway is associated with positive symptoms of schizophrenia
17
Q
What is the mesocortical pathway of the dopaminergic system?
A
- Mesocortical pathway projects from the ventral tegmental area to the prefrontal cortex
- Involved in motivation, emotion & other cognitive functions
18
Q
What is the tubero-hypophyseal pathway of the dopaminergic system?
A
- Dopamine is released from the hypothalamus & transported to pituitary via circulation
- Acts to inhibit prolactin release
19
Q
What are the functions of dopamine?
A
- Movement
- Reward
- Vomiting
- Addiction
- Inhibition of prolactin release
20
Q
Give some examples of disorders of the dopaminergic system?
A
- Parkinson’s, ADHD, Schizophrenia, Emesis
21
Q
Describe dopamine synthesis & storage
A
- Dopamine is synthesised from Tyrosine
- Tyrosine -> L-DOPA -> Dopamine
- Tyrosine -> L-DOPA by Tyrosine hydroxylase
- L-DOPA -> Dopamine by Dopa decarboxylase
- Store in vesicles by VMAT (Vesicular Monoamine transporter)
22
Q
What are the two classes of dopamine receptor?
A
- D1-like receptor - stimulate AC
2. D2-like receptor - inhibit AC
23
Q
What are the sub-types of the Dopamine receptors?
A
- D1-like receptors have two sub-types: D1 & D5
- D2-like receptors have three sub-types: D2, D4, D3
24
Q
What is the mechanism of action for D1-like receptors?
A
- D1 like receptors are Gs protein receptors that stimulate adenylate cyclase
- Adenylase cyclase increases cAMP formation.
- cAMP activates PKA (Protein Kinase A) which phosphorylates a dopamine signalling molecule called DARPP-32
25
What is the mechanism of action for D2-like receptors?
- D2 like receptors can be located post & pre-synaptically
- D2 like receptors are coupled to Gi/o so they inhibit adenylate cyclase to decrease DA by causing K+ efflux leading to hyperpolarisation
- D2 & D3 receptors can act as autoreceptors
26
Describe the re-uptake & degradation of dopamine
- Dopamine re-uptake occurs by DAT
- Dopamine can be metabolised by an isoenzyme of monoamine oxidase known as MONOAMINE OXIDASE B
- Dopamine can also be degraded by CATECHOL-O-METHYLTRANSFERASE
27
Give three ways in which dopamine levels can be increased e.g to treat a disorder
1. Administer a pre-cursor of dopamine such as L-DOPA which can be metabolised into dopamine
2. Block the dopamine re-uptake transporters (DAT) to cause dopamine accumulation
3. Inhibit monoamine oxidase B to prevent the degradation of dopamine
28
What are the neuronal cell bodies of the serotonergic system & it's projections?
- The serotonergic system uses serotonin as it's neurotransmitter
- Serotonergic neurones project from the raphe nuclei to areas such as the cortex, striatum, thalamus, hypothalamus, spinal cord etc.
29
**Describe the synthesis & storage of serotonin?
- Serotonin is synthesised from L-tryptophan
- L-tryptophan -> 5-hydroxL-tryptophan -> Serotonin
- L-tryptophan -> 5-hydroxyL-tryptophan by TRYPTOPHAN HYDROXYLASE
- 5-hydroxyl-L-tryptophan -> Serotonin by DOPA DECARBOXYLASE or L-AROMATIC ACID DECARBOXYLASE
- Serotonin is transported into vesicles by VMAT
30
Describe the re-uptake & degradation of serotonin
- Serotonin is taken up from the synaptic cleft by SERT (Serotonin re-uptake transporters)
- Serotonin is degraded by Monoamine oxidase
31
What are the functions of serotonin?
1. Mood
2. Sleep/Wake
3. Appetite
32
Give two ways to increase serotonin
1. Block the SERT - to prevent re-uptake of serotonin
| 2. Inhibit Monoamine Oxidase to prevent serotonin breakdown
33
Describe the properties of serotonin receptors
- Serotonin receptors are typically located post-synaptically
- There are 14 subtypes of the Serotonin receptor, they are all G-protein coupled receptors except for 5HT3 which is LIGR
34
What are the effects of 5HT1-7 receptors?
1. 5HT1 - excitatory, limbic system -> mood, migraine
2. 5HT2 - excitatory, limbic system & cortex
3. 5HT3- excitatory, medulla, vomiting - found in teh chemoreceptor trigger zone, blocking it causes anti-emetic effect
4. 5HT4 - pre-synaptic facilitation
5. 5HT6&7 - Cognition, sleep
35
What are the autoreceptors for serotonin, dopamine & NA?
```
Serotonin = 5HT1D
Dopamine = D2 & D3
NA = alpha 2
```
36
What are the re-uptake transporters for serotonin, dopamine & NA?
```
Serotonin = SERT
Dopamine = DAT
NA = NERT/NET
```
37
What are the neuronal cell bodies of the cholinergic neurones & it's projections?
- The cholinergic system uses acetylcholine as it's neurotransmitter
- The neuronal cell bodies are located in the basal forebrain & the brain stem complexes (striatal interneurones), which project out to cortex, hippocampus & hypothalamaus
38
What are the functions of acetylcholine?
1. Memory, learning
2. Motor control -striatum
3. Reward
4. Arousal
5. Modulation of pain
39
How is acetyl choline synthesised & stored?
- Acetyl choline is synthesized by combing Acetyl CoA & Choline using the enzyme CHOLINE ACETYL TRANSFERASE
- Acetyl choline is transported into vesicles by VAchT
40
Describe the degradation & re-uptake of acetylcholine
- Acetyl CoA is degraded into acetate & choline by choline esterases
- The choline is then taken up by choline carriers
41
What are some disorders of the cholinergic system?
- Schizophrenia, epilepsy, ADH, depression, anxiety, addiction
42
Give two ways that disorders of the cholinergic system can be treated?
1. ANTICHOLINESTERASES - inhibit the breakdown of acetylcholine known as Neostigmine
2. Prevent the re-uptake of choline e.g Hemicholinium
43
What are the two classes of Ach receptors?
1. LIGR/NICOTINIC ACETYLCHOLINE RECEPTOR
| 2. G-PROTEIN/ MUSCARINIC ACETYCHOLINE RECEPTOR
44
What are the 5-subclasses of muscarinic receptors & what do they do?
M1 - excitatory
M2 - pre-synaptic inhibition
M3 - excitatory smooth muscle effects
M4 & M5
45
What are the effects/consequences of amphetamine?
- Increases NA or DA:
- Increase alertness or aggression
- Euphoria/excitement
- Increased confidence or lack of tiredness
- Anorexia
- E.g MDMA (ecstasy), methylphenidate
- Acts as an appetite suppressant & used to treat narcolepsy
