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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
What does PKA regulate the transcription of?
-c-fos - brain derived neurotrophic factor (BDNF) - Tyrosine Hydroxylase (TH) - Neuropeptides: somatostatin, enkephalin, VGF, CRH, PER1, PER2, etc.
26
In some cases, D2 receptors also regulate ..... on the post synaptic membrane
K+ channels
27
The clinical potency of antipsychotic medication is a function of the drugs.... to the .... receptor
affinity, D2
28
Catecholamines are broken down and recycled in how many different ways?
7
29
Reuptake process
- 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
Enzymatic degradation process
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
Why is the mesolimibic pathway regarded as the reward pathway
Stimulating neurons in the VTA results in dopamine release onto the nucleus accumbens (the reward centre), which leads to a feeling of euphoria.
32
What happens when dopamine is released onto the nucleus accumbens
other brain regions are activated
33
can "reward" be quantified
yes
34
how can you measure neurotransmitters release in a given brain region
micro dialysis
35
Dopamine hypothesis of schizophrenia
hyperactivity of dopaminergic transmission at the D2 receptor contributes to the condition.
36
The main pathological hallmark of Parkinson's disease and what does this result in?
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
where does the conversion of tyrosine to dopamine occur
predominantly in the cytoplasm
38
where does the conversion of dopamine to norepinephrine occur
predominantly inside vesicles
39
epinephrine is synthesized by cells in the......
adrenal medulla
40
Effects of peripheral epinephrine:
-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
Central and peripheral components to the noadrenergic system
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
The Locus Coeruleus (LC) contains.....
a dense cluster of noradrenergic neurons.
43
Cells in the adrenal medulla synthesize and release...
epinephrine
44
Following the release of norepinephrine and/or epinephrine into the blood stream, these hormones will seek out and bind to...
adrenergic receptors
45
two main types or adrenergic receptors
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
What do beta blockers do?
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
Can peripheral norepinephrine/epinephrine influence brain activity?
yes
48
How can epinephrine affect brain activity
via the vagus nerve
49
Peripheral epinephrine has been shown to increase .....
central norepinephrine release
50
One function of peripheral epinephrine’s actions on the brain is to....
facilitate the consolidation of memories. Specifically, emotional memories.
51
passive avoidance learning
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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