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Molecular Neuroscience I > 3 - NA, DA, 5-HT and HA > Flashcards

3 - NA, DA, 5-HT and HA Flashcards

1
Q

What does NA stand for?

A

Norepinephrine

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2
Q

What does DA stand for?

A

Dopamine

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3
Q

What does HA stand for?

A

Histamine

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4
Q

What is a catecholamine?

A

A catecholamine (CA) is a monoamine, an organic compound that has a catechol (benzene with two hydroxyl side groups) and a side-chain amine.

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5
Q

What amino acid do all catecholamines derive from?

A

Tyrosine

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6
Q

What are the three most common catecholamines in the body?

A
  • Dopamine
  • Norepinephrine
  • eprinephrine
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7
Q

What are the three types of adrenergic receptors and what G proteins are they coupled to?

A
  • α1 (Gq)
  • α2 (Gi)
  • β(1,2,3) (Gs)
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8
Q

Write the synthesis paths of the catecholamines from tyrosine to epinephrine and the enzymes involved (4 steps/enzymes)

A
  1. Tyrosine to L-DOPA (tyrosine hydroxylase)
  2. L-DOPA to dopamine (AADC - aromatic L-amino acid decarboxylase)
  3. Dopamine to norepinephrine (dopamine β-hydroxylase DβH)
  4. Norepinephrine to adrenaline (PNMT - phenylathanolamine-N-methyltransferase)
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9
Q

Name the transporters involved in the synthesis of catecholamines from L-DOPA to degradation by monoamine oxidase.

A
  1. L-DOPA is transported into a vesicle by VMAT (vesicular monoamine transporter)
  2. norepinephrine in a synapse is reuptaken by NET (norepinephrine transmembrane transporter). It is then either shuttled into a vesicle by VMAT or degraded by monoamine oxidase
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10
Q

Where do norepinephrine containing neurons arise in the brain?

A

The locus coeruleus in the brainstem

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11
Q

Where can norepinephrine be found in the brain?

A

Everywhere

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12
Q

Where can norepinephrine by found in the PNS?

A

Most postganglionic neurons of the sympathetic system

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13
Q

What type of feedback mechanism prevents over stimulation of β-adrenergic receptors?

A

A negative feedback loop

  1. G protein-coupled receptor kinase (GPK) phosphorylates the receptor that then becomes a target for arrestins
  2. β-arrestin (βARR) promotes receptor internalization of the receptor by binding to clathrin
  3. Clathrin starts endocytosis of the receptors (the receptor can then be recycled or degraded)

This is a negative feedback loop because agonists of the β-adrenergic receptor cause this

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14
Q

What happens to mice lacking dopamine β-hydroxylase (DβH)?

A

They are unable to synthesize norepinephrine and epinephrine, and so lack response to serotonergic antidepressents

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15
Q

Where do the two most important dopamine tracts originate?

A

The midbrain

  • Nigrostriatal
  • Mesolimbic
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16
Q

What is the nigrostriatal tract?

A

A dopamine tract that connects the substantia nigra in the midbrain with the basal ganglia below the cortex.

Damage causes Parkinson’s disease

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17
Q

What is the mesolimbic tract?

A

A dopaminergic tract that arises from the ventral tegmental area (VTA) and projects to limbic structures such as the ventral striatum, nucleus accumbens, amygdala and the cortex

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18
Q

True or false? All known dopaminergic receptors are metabotropic.

A

True

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19
Q

How can alternative splicing create different variants of dopamine receptors?

A

D1-like receptors: No introns

D2-like receptors: Introns present

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20
Q

What are the two dopamine receptor subtypes and the receptors within these subtypes?

A

D1-like: D1, D5

D2-like: D2, D3, D4

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21
Q

What G proteins are coupled to D1-like dopamine receptors?

A

Gs

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22
Q

What G proteins are coupled to D2-like dopamine receptors?

A

Gi/o

23
Q

True or false? Dopaminergic activity increases with age.

A

False. Dopaminergic activity decreases with age.

24
Q

What happens to mice with the D1 dopamine receptor gene knocked out?

A
  • Growth retarded
  • Not interested in drinking and feeding
  • Lack of locomotor activation after cocaine.
  • Abnormal development of the striatum
25
Q

What happens to mice with the D5 dopamine receptor gene knocked out?

A

Higher than normal locomotor activity, response to cocaine not altered

26
Q

What happens to mice with the D2 dopamine receptor gene knocked out?

A

Decreased locomotor activity, response to cocaine not altered.

27
Q

What happens to mice with the D3 dopamine receptor gene knocked out?

A

Increased locomotion in novel environments. Supersensitive to cocaine and amphetamines

28
Q

What happens to mice with the D4 dopamine receptor gene knocked out?

A

Reduced locomotor behaviour. Supersensitive to the locomotor stimulating effect of cocaine and emphetamine

29
Q

What happens to mice with the D1, D3 and D5 dopamine receptor genes knocked out?

A

Mice develop hypertension, indicating a role for these dopamine receptors in blood pressure control

30
Q

How do neuroleptics treat psychosis in schizophrenia as well as Huntingtons and Alzheimers? What is a common side effect?

A

These block the activity (antagonists) of D2-like dopamine receptors

This can cause Parkinson’s like effects by acting on the nigrostriatal pathway

31
Q

L-DOPA is commonly used to treat Parkinson’s Disease. What are some ways to boost treatment effectivity?

A
  • Blocking peripheral aromatic amino acid decarboxylases so that dopamine is synthesized in the brain and L-DOPA is not used up in the periphery
  • Selective MAO inhibitors
  • Selective COMT (Catechol-O-methyl transferase) inhibitors (inhibits degradation of catecholamines)
32
Q

Where do serotonin containing neurons arise from in the brain?

A

The raphe nuclei, part of the reticular formation in the upper brainstem. These distribute widely throughout the brain

33
Q

Describe the serotonin synthesis pathway (2 steps and enzymes)

A
  • Tryptophan to 5-hydroxytryptophan (5-HTP) (by tryptophan hydroxylase)
  • 5-HTP to serotonin (by L-aromatic amino acid decarboxylase)
34
Q

What enzyme degrades serotonin and what is the resulting metabolite?

A

MAO and aldehyde dehydrogenases

Result is 5-hydroxyindoleacetic acid (5-HIAA )

35
Q

There are 7 serotonergic receptors, which one is inhibitory? Which one is ionotropic?

A

5-HT1 (5-HT2-7 are all excitatory)

5-HT3 is ionotropic (rest are metabotropic)

36
Q

What is often a symptom associated with decreased serotonin 5-HT1a receptors?

A

Depression

37
Q

What are 5-HT1b receptor agonists being used for?

A
  • Migraine treatment
38
Q

LSD and other hallucinogens produce hallucinations by activating ____?

A

5-HT2a serotonin receptors

39
Q

What happens in mice with the 5-HT2c serotonin receptor knocked out?

A

Spontaneous convulsions, cognitive impairment, increased food intake and obesity.

40
Q

What are 5-HT3 receptor antagonists used for?

A

Treatment of hemotherapy and radiotherapy induced nausea and vomiting

41
Q

What are selective 5-HT6 serotonin receptor antagonists and agonists commonly used for?

A

Treating memory impairment and cognition (antagonists)

Treating anxiety and depression (agonists)

42
Q

What are SSRIs?

A

selective serotonin reuptake inhibitors, inhibit 5-HT transporters`

43
Q

Serotonin 2C agonists or antagonists may be used to treat obesity?

A

Agonists

44
Q

What transporter shuttles histidine into neurons?

A

L-amino acid transporter

45
Q

What must happen to histamine before it is available for secretion into a neural synapse?

A
  • Histidine is transported into the neuron with L-amino acid transporter
  • Histidine is converted to histamine by histidine carboxylase
  • Histamine is packaged into vesicles with vesicular monoamine transporter
46
Q

What enzyme breaks down secreted histamine?

A

Histamine methyltransferase

47
Q

What are the 2 most common non-neuronal actions of histamine?

A
  • Stimulation of immune response (H1 receptor)

- Gastric acid secretion (H2 receptor)

48
Q

Where do histaminergic neurons in the brain originate from?

A
  • Tuberomamillary nuclei in the hypothalamus

- Mast cells in thalamus

49
Q

What are two types of drugs affecting histaminergic receptors?

A

Antagonists against H1 (asthma) and H2 (gastric ulcers)

50
Q

What histaminergic receptor knockout produced lower day to night locomotion ratio?

A

H1 and H3

51
Q

What histaminergic receptor knockout produced obesity?

A

H3

52
Q

What transmitter is often present in food and metabolized by diamine oxidase (DAO)?

A

Histamine

53
Q

What is the difference between 5-HTP and 5-HT?

A

5-HTP: 5-hydroxytryptophan

5-HT: Serotonin

L-aromatic amino acid decarboxylase can convert 5-HTP into serotonin. Serotonin cannot cross the blood brain barrier, but 5-HTP can.

Molecular Neuroscience I (8 decks)

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