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Medsci 307 > neurotransmitters > Flashcards

neurotransmitters Flashcards

1
Q

What are noradrenaline and serotonin and what are they derived from?

A

They are monoamine and are derived from dietary amino acids like tyrosine and tryptophan

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2
Q

What re the 3 distinct properties of noradrenaline and serotonin?

A

Axons arise from cell bodies in distinct subcortical nuclei from a few hundred cells.

  1. axons branch out extensively to innervate most parts of the cortex and other brain regions
  2. They produce a combination of inhibitory and excitatory effects which are generally NEUROMODULATORY.
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3
Q

How is noradrenaline synthesised?

A

Tyrosine is metabolised by tyrosine hydroxylase to dopa and dopa to dopamine by dopa decarboxylase. Dopamine to noradrenaline via dopamine beta hydroxylase.

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4
Q

Where is dopamine beta hydroxylase found?

A

only in noradrenaline neurons not dopamine neurons.

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5
Q

Where is noradrenaline stored?

A

70% of it is stored in vesicles while the rest is in the cytoplasm.

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6
Q

What is noradrenaline release dependent on?

A

Calcium

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7
Q

What are the two processes that inactivate noradrenaline?

A

reuptake and metabolism

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8
Q

What is the pathway to metabolise noradrenaline?

A

noradrenaline is metabolised by COMT and MAO
MAO is found in mt neurons and glia
COMT found in extracellulary

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9
Q

Where does nore go and how?

A

Nore is found in locus ceruleus in the brainstem that is on both sides. The axon from locus ceruleus go to the hypothalamus, thalamus, hippocampus, cerebral cortex, cerebellum via the dorsal noradrenergic bundle.

Brainstem nuclei is the descending pathways to the spinal cord.

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10
Q

What are the functions of nore?

A 
chane potassium conductance couple with facilitation of responses to other neurotransmitters
attention and learning
blood pressure regulation
thermoreglation
pain control in spinal cord
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11
Q

What are the receptors of nore?

A

a1A - increase in calcium
a1B - increase IP3/DAG
a2A and a2B - decrease in cAMP
B1.2.3 - increase in cyclic AMP

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12
Q

How is serotonin synthesised?

A

L-tryptophan metabolised by tryptophan hydroxylase to 5-hydroxytryptophan then 5 hydroxytryptamine via L-aromatic acid decarboxylase.

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13
Q

Where is serotonin stored?

A

vesicles

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14
Q

How is serotonin released?

A

fusion of vesicles to cell membrane and it is calcium dependent

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15
Q

What are the two methods that sero is inactivated?

A

reuptake and metabolism

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16
Q

What is the pathway to metabolise sero?

A

5-HT via MAO to 5-HIAA

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17
Q

How is sero taken bck into neurons?

A

high - affinity active transport that prozac can target

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18
Q

Where is sero localised?

A

cell bodies containing 5-HT are clustered in the midline region of the brainstem in an area called the raphe nuclei. From the nuclei projections go to the basal ganglia, hipposcampus, cortex and cerebellum.
Descending projections to the spinal cord.

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19
Q

What are the functions of serotonin?

A

sleep, mood control (antidepressants), appetite, anxiety, analgesia (pain killer). VERY important to depression and anxiety

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20
Q

What are the receptors of serotonin?

A

5-HT 1A/ 1B / 1D = decreases cAMP
5-HT 2 / 1C - increases IP3/DAG post synaptic only for 2
5-HT 3 - modulates neurotransmitter release (modulates dopamine systems)

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21
Q

What is the metabolism pathway of dopamine?

A

Tyrosine to dopa via tyrosine hydroxylase and dopa to dapamine to dopa decarboxylase.

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22
Q

Where is dopamine stored?

A

75% are stored in vesicles from MAO.

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23
Q

How is dopamine released?

A

Calcium dependent
fusion with membrane.
it can be released from axon and dendrites in SNPc

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24
Q

What is the metabolic pathway that inactivates dopamine?

A

dopamine to DOPAC via MAOb and DOPAC to Homovanillic acid via COMT.
dopamine to 3 methoxytryramine via COMT and that to homovanillic acid via MAOb.

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25
Q

Where is the largest concentration of dopamine?

A

Basal ganglia and limbic system

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26
Q

What does dopamine affect?

A

mood, movement and emotions.

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27
Q

What are the 3 main dopaminergic pathways?

A

Nigro-striatal
Mesolimbic or Mesococtical system pathway
Hypothalamic pathway

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28
Q

Describe the nigrostriatal pathway. This pathway is lost in which neurodegenerative disease?

A

SNPc part of the extrapyramidal motor system which go to striatum releasing dopamine. This pathway is lost in PARKINSONS.

29
Q

Describe where the cell bodies of the mesolimbic pathway are

A

ventral tegmentum part of the midbrain has cell bodies in it and some in SNPc.

30
Q

Describe where the mesolimbic pathway cell bodies go to.

A

ventral or lower striatum
limbic system
frontal cortex

31
Q

The mesolimbic pathway is overactive in which neurodegenerative disease?

A

SCHIZOPHRENIA

32
Q

What is the hypothalamic pathways involved in?

A

hypothalamic

33
Q

What does the D1 receptor do?
What is the antagonist of the D1 receptor?
Which other receptor is this receptor like?

A

increases cAMP
post synaptic in the striatum and substantia nigra. Linked to Gs
ANTAGONIST = SCH23390
D5

34
Q

What does the D2 receptor do?

Where is it present?

A

reduces cAMP and phosphatidylinositol
linked to Gi
presynaptic in the nigrostriatal and corticostriatal pathways
post synaptic in the striatum and SNC

35
Q

What is the antagonist of the D2 receptor?

A

sulpiride

36
Q

D3 and D4 are similar. What is their function and where are they present?
What other receptor is it similar to?

A

low levels in striatum
high in limbic system, nucleus accumbens and pre-frontal cortex.
D2 but anatomically different to it.

37
Q

What is the function of dopamine in terms of inhibition and excitation?

A 
inhibitory and excitatory effects in the striatum by releasing dopamine tonically. 
inhibits neuronal firing = 
* amygdala
*pre-frontal cortex
*nucleus accubens
38
Q

how does dopamine increase motor control?

A

the agonist increase movement via D1 and D2 activation in the striatum.

39
Q

What other functions does dopamine control that also contributes to schizophrenia?

A

mood and psychosis

40
Q

How does dopamine cause vomiting?

A

dopamine receptors in the chemo-receptor trigger zone in brainstem produce vomiting.

41
Q

What does dopamine control in the thalamus

A

neuroendocrine control

42
Q

How does dopamine cause drug dependence?

A

release of dopine in the nucleus accumbens mediates brain reward and so is involved in drug dependence.

43
Q

How does cocaine cause cocaine dependence?

A

cocaine increases dopamine in the synaptic cleft in the nucleus accumben because it binds to the dopamine transporter. This causes the cocaine high thus a cocaine dependence.

44
Q

What is cocaine addiction evident by?

A

cravings, cocaine seeking behaviour.

45
Q

What enhances cocaine seeking behaviour?

A

D1

46
Q

What decreases cocaine craving?

A

D2

47
Q

What are the neurotransmitters that are important constituents of diet and are involved in a number of metabolic processes?

A

Glutamate and aspartate

48
Q

How do you synthesize glutamate?

A

glutamine via glutaminase to glutamate!!!!

49
Q

How do you store glutamate and aspartate?

A

formed inthe cytoplasm and stored in nerve terminals

50
Q

What is the release of glutamate and aspartate dependent on?

A

Calcium dependent

51
Q

How is glutamate and aspartate effect inactivated via reuptake?

A

Reuptake into neurons and glia via HIGH AFFINITY SODIUM depedent process and a low affinity uptake which is associated with other aa aswell.

52
Q

How is glutamate inactivated via enzyme degradation?

A

glutamate metabolised in the glia via glutamine synthetase glutamine. Glutamine is then released from glia and taken up by neurons and it is recycled in the neurons to glutamate.

53
Q

What are the pathways glutamine goes throught to have an effect?

A

Coticofugal
Allocortical
Primary afferent to dorsal horn of the spinal cord
Cortico-cortical projections (Commisural fibres)

54
Q

What are the three different sub pathways for glutamine?

A

cortico-striatal
entorhinal cortex to hippocampus
visual cortex to lateral geniculate and superior colliculus

55
Q

What is the allocortical pathway that glutamine uses?

A

hippocampus to lateral septum

56
Q

What are the functions of glutamate

A 
Glutamate depolarizes the neurons. 
Glutamate is the main excitatory neurotransmitter affecting:
1. cognition
2. memory
3. movement
4. sensation
5. emotion
57
Q

How does glutamate activate ampa receptors?

A

glutamate binds to AMPA receptor causing sodium influx causing neuronal depolarisation

58
Q

What are the multiple subunits that compose the AMPA receptors?

A

GluR1-4.
GluR2 allows sodium NOT CALCIUM
GluR3 - carries ca ions
if you have ISCHAEMIC brain injury causing a decrease GluR2 then ca entry increases causing brain damage.

59
Q

What are the agonists of AMPA receptors?

A

AMPA, glutamate, kainate

60
Q

What is the antagonist of AMPA and Kainate receptors

A

NBQX

61
Q

Kainate receptor process?

A

same as AMPA receptor.

sub nits are GluR5-7

62
Q

How do metabobotropic receptors Group 1 (mGluR1 and 5) work?

A

glutamate attaches to mGluR 1 and 5 activating phospholipase C. This activates the G protein linked secondary messengers IP3 and DAG. These cause increased intracellular in the cytoplasm from intracellular stores and increased protein kinase C.

63
Q

How do Group 2 (mGluR2 and 3) work?

A

Gi-linked and inhibit adenylate cycle and cause presynaptic decrease in neurotransmitter release. Agonists at these receptors are neuroprotective in model systems by inhibiting glutamate release or activating the production of endogenous neuroprotective molecules (TGFbeta1) by astrocytes.

64
Q

What is significant about NMDA receptors?

A

voltage and ligand (calcium) gated

65
Q

What are the 5 binding sites of NMDA receptors?

A

NMDA/glutamate binding site causes increased ca influx

Strychine INsensitive glycine binding site which attaches glycine consequently increasing the prob of channel opening acting as a coagonist.

Phencyclidine binding site decreasing channel action (non competitive antagonist) by binding OPEN channel.

Zinc binding site inhibiting receptor function

Polyamine site enhance binding of open channel blockers

66
Q

What prevents calcium entry into NMDA receptors?

A

magnesium ions

67
Q

How does calcium enter through the NMDA receptors?

A

depolarization causes removal of mag and entrance of ca

68
Q

What are the negative effects of glutamate?

A

epilepsy and stroke
head injury and neurodegenerative disease
Schizophrenia (PCP) and drug dependence
Glioma formation

Medsci 307 (4 decks)

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