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Neuropharm lecture 1 > Neuropharm lecture 3- catecholamines > Flashcards

Neuropharm lecture 3- catecholamines Flashcards

1
Q

What are Catecholamines?

A

a class of neurotransmitters that all have a similar chemical makeup

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2
Q

What is the structure of Catecholamines?

A

a benzene ring with two hydroxyl groups, an ethyl chain, and a terminal group. All Catecholamines have a catechol nucleus and one amine group.

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3
Q

What group of neurotransmitters do Catecholamines belong to?

A

monoamines

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4
Q

How many types of Catecholamines are there and what are they?

A

3 types; Dopamine, Norepinephrine, and Epinephrine.

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5
Q

What is the first catecholamine to be synthesized

A

Dopamine

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6
Q

What enzyme is Tyrosine modified by

A

Tyrosine hydroxylase

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7
Q

What is Tyrosine Hydroxylase and what does it do?

A

TH is the rate limiting step in production of all Catecholamines. TH has a negative feedback loop, where high levels of catecholamines inhibit TH.

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8
Q

Where is Tyrosine Hyrdroxylase found?

A

found in cytosol of all cells containing catecholamines

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9
Q

Dopamine is a precursor to … and …

A

norepinephrine and epinephrine

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10
Q

Where is the major source of dopamine in the CNS?

A

the midbrain

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11
Q

What pathways are the midbrain dopamine neurons separated into?

A
  1. Nigrostriatal pathway
  2. Mesolimbic/Mesocortico pathway (mesocorticolimbic pathway)
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12
Q

Nigrostriatal pathway

A

plays an essential role in the control of voluntary motor movement.

Implicated in diseases of the motor system

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13
Q

What diseases of the motor system is the nigrostriatal pathway implicated in?

A
  • Parkinsons disease
  • Huntington disease
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14
Q

Mesolimbic pathway

A

The reward system

implicated in substance use and addiction

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15
Q

What are all catecholamines, dopamine included, released by?

A

exocytosis

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16
Q

When is exocytosis released?

A

When a nerve impulse reaches the terminal.

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17
Q

What drives the release of dopamine in the absence of action potentials?

A

Amphetamines and methamphetamines

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18
Q

How many receptor subtypes does dopamine use and what are they?

A

D1-D5, they are all metabotropic receptors

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19
Q

What can D2 receptors function as?

A

auto receptors and postsynaptic receptors

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20
Q

Does D1 and D2 receptors have similar or opposite effects?

A

opposite

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21
Q

What does D1-like activation do?

A

stimulates adenylyl cyclase and cAMP synthesis

22
Q

What does D2-like activation do?

A

inhibits adenylyl cyclase and cAMP synthesis

23
Q

What does cAMP do?

A

serves as a signal to initiate the protein kinase A second messenger cascade.

24
Q

What do PKA catalytic subunits do?

A

dissociate and influence activity of ion channels, regulation of receptor expression on membrane, metabolism, etc.

25
Q

What does PKA regulate the transcription of?

A

-c-fos
- brain derived neurotrophic factor (BDNF)
- Tyrosine Hydroxylase (TH)
- Neuropeptides: somatostatin, enkephalin, VGF, CRH, PER1, PER2, etc.

26
Q

In some cases, D2 receptors also regulate ….. on the post synaptic membrane

A

K+ channels

27
Q

The clinical potency of antipsychotic medication is a function of the drugs…. to the …. receptor

A

affinity, D2

28
Q

Catecholamines are broken down and recycled in how many different ways?

A

7

29
Q

Reuptake process

A
  • DA and NE are removed from the synaptic cleft, back into the nerve terminal via transporter proteins embedded on the pre synaptic membrane.
  • Transporter proteins take advantage of concentration gradients for ions to drive catecholamines back into synaptic cleft.
  • Molecules are then re-packaged into vesicles ready to be released, or they are broken down into building blocks and recycled.
30
Q

Enzymatic degradation process

A

Breakdown of catecholamines via:
- COMT which is located In the synaptic cleft
- MAO, which is located in the pre-synaptic terminal

Once these enzymes get a hold of dopamine, they break it down into a metabolite called HVA

HVA enters the CSF and the bloodstream and is eliminated in urine.

31
Q

Why is the mesolimibic pathway regarded as the reward pathway

A

Stimulating neurons in the VTA results in dopamine release onto the nucleus accumbens (the reward centre), which leads to a feeling of euphoria.

32
Q

What happens when dopamine is released onto the nucleus accumbens

A

other brain regions are activated

33
Q

can “reward” be quantified

A

yes

34
Q

how can you measure neurotransmitters release in a given brain region

A

micro dialysis

35
Q

Dopamine hypothesis of schizophrenia

A

hyperactivity of dopaminergic transmission at the D2 receptor contributes to the condition.

36
Q

The main pathological hallmark of Parkinson’s disease and what does this result in?

A

a progressive loss of dopaminergic neurons in the substantia nigra.

It results In severe dopamine depletion in the nigrostriatal dopamine pathway.
- responsible for motor symptoms associated with PD.

37
Q

where does the conversion of tyrosine to dopamine occur

A

predominantly in
the cytoplasm

38
Q

where does the conversion of
dopamine to norepinephrine occur

A

predominantly inside vesicles

39
Q

epinephrine is
synthesized by cells in the……

A

adrenal medulla

40
Q

Effects of peripheral epinephrine:

A

-Increased rate and force of heart
contractions;
- Constriction of blood vessels  increase
blood pressure;
- Dilation of bronchioles  assists in
pulmonary ventilation;
- Promotes breakdown of glycogen in
skeletal muscle;
- Dilation of pupils  improved vision (in
low light

41
Q

Central and peripheral components to the noadrenergic system

A

Central:
- Cell bodies in the brain stem with ascending fibers reaching many
forebrain structures;
- Noradrenergic neurons can also extend to the periphery and form
synaptic connections with organs (e.g. synapse with cardiac
cells).
Peripheral:
- Part of the sympathetic nervous system (main driver);
- Many neurons in the SNS use norepinephrine as their transmitter;
- Norepinephrine can also be synthesized and released from the
adrenal glands directly into the blood stream (cannot cross BBB!)

42
Q

The Locus Coeruleus (LC) contains…..

A

a dense cluster of noradrenergic
neurons.

43
Q

Cells in the
adrenal
medulla
synthesize and
release…

A

epinephrine

44
Q

Following the release of norepinephrine and/or epinephrine into the blood
stream, these hormones will seek out and bind to…

A

adrenergic receptors

45
Q

two main types or adrenergic receptors

A

alpha and beta

α1 operate via phosphoinositide 2nd messenger system;
- α2 receptors reduce synthesis of cAMP (like D2-like);
- b1 and b2 stimulate adenylyl cyclase and enhance synthesis of cAMP (like D1-like

46
Q

What do beta blockers do?

A

prevent the normal binding to the
beta-adrenoreceptor by competing for the binding
site.

Can be used to reduce symptoms of a fight or flight
response (pounding heart, cold/clammy hands,
increased respiration, sweating, etc

47
Q

Can peripheral norepinephrine/epinephrine
influence brain activity?

A

yes

48
Q

How can epinephrine affect brain activity

A

via the vagus nerve

49
Q

Peripheral epinephrine has
been shown to increase …..

A

central norepinephrine release

50
Q

One function of peripheral epinephrine’s
actions on the brain is to….

A

facilitate the
consolidation of memories. Specifically,
emotional memories.

51
Q

passive avoidance learning

A

animals avoid an aversive stimulus by inhibiting a previously punished response. Unless, we give them B-
blockers during the training trials. They
will not remember which side they
were shocked on and spend equal
amounts of time in both compartments
during testing.

Neuropharm lecture 1 (3 decks)

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