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Flashcards in Advanced Midterm Review Deck (81):
1

What are the amine neurotransmitters? (6)

- Acetylcholine
- Norepinephrine
- Epinephrine
- Dopamine
- 5-HT (serotonin)
- GABA

2

What are the amino acid NTs? (3)

- Glutamate
- Glycine
- Aspartate

3

What are the purine NTs? (2)

- ATP
- Adenosine

4

What are the gas neurotransmitters? (3)

- Nitric Oxid
- Carbon monoxide
- Hydrogen sulfide

5

What are the two precursors of glutamate?

- alpha-ketoglutarate
- Glutamine

6

What percent of clinically marketed drugs are modulates of metabotropic receptors?

30%

7

What is the consequence of a missense mutation in the GNAS1 gene?

- McCune-Albright syndrome
- This gene encodes the Gsα subunit of G protein
- Mutation results in downregulation of cAMP signalling, causing deformity of bones, different pigment patches (cafe-au-lait) hormones hypersecretion and early puberty

8

How can receptors coupled to G protein cause Alzheimer's disease?

With abnormal function of receptors coupled to G proteins, especially those involved in phosphoinositide hydrolysis

9

What is myasthenia gravis caused by? (3)

- Result of decreased nAChr expression in the postsynaptic site of neuromuscular junctions

- Caused mostly by T-lymphocyte dependent autoimmune reaction against nACHRs
or
- Hereditary mutation of ε-subunit of nAChR

10

What is juvenile myoclonic epilepsy?

- An effect of missense mutation of the GABAa receptor α1 subunit,
- Accounts for 5-10% of all epilepsy patients

11

What are SH2 domains?

Src homology 2 - tyrosine binding domains

Proteins with these domains bind to phosphorylated tyrosines. They include enzymes such as PLC, IP3-Kinase and adaptor proteins such as growth receptor binding protein-2

12

What is an example of an intracellular receptor?

Glucocorticoid receptors

- The steroid receptor is retained in the cytoplasm by binding to HSP90
- Following ligand binding (with NO, H2S etc.) HSP90 is released and the receptor translocates to the nucleus.
- Steroid receptors bind to steroid response elements on DNA and result in upregulation of anti-inflammatory genes and downreguation of inflammatory cytokines

13

In the cerebral cortex, cholinergic synapses account for about ___ % of the total synaptic population

5-7%

14

What enzyme synthesizes acetylcholine?

Choline acetyl transferase (ChAT)

15

What is the homomeric nicotinic ACh receptor comprised only of α7 subunits characterized by?

High calcium ion permeability

16

What do α5 nicotinic receptor subunits do? Mutation of the gene encoding this subunit does what?

Controls nicotine intake

- Mutation of the CHRNA5 gene causes increased nicotine consumption.
- Also at higher risk for cancer and obstructive pulmonary disease.
- Neurons in the medial habenula are responsible for these effects.

17

What do α7 nicotinic subunit knockouts show?

Deficit in attention and working episodic memory.

18

What do β2 nicotinic receptor subunit -/- knockout mice show?

Model for sudden infant death syndrome (SIDS)

19

What percent of synapses in the brain are glutamatergic?

40%

20

True or false? There are more glutamate metabotropic receptors than ionotropic receptors

True.

8 metabotropic
3 ionotropic

21

What are ketamines used for? And what are they?

NMDA antagonist

Used for anaesthesia, with some neuroprotective functions

22

What Is dextromethorphan? What is it used for?

NMDA antagonist

Used as a cough suppressent

23

What is dizocilpine? What is it used for?

MK-801 NMDA receptor antagonist

Used to make animal models of schizophrenia and used for stroke and alzheimer's prevention

24

Which metabotropic glutamate receptors are located postsynaptically? (2)

mGluR1 and mGluR5

25

Which metabotropic glutamate receptors are located presynaptically? (5)

mGluR2,3,4,7,8

26

Which metabotropic glutamate receptors are linked to Gq proteins? (2)

Group I

- mGluR1
- mGluR5

27

Which metabotropic glutamate receptors are linked to Gi/o proteins? (6)

Group II and III

- mGluR2,3 (Group II)
- mGluR4,6,7,8 (Group III)

28

Which type of receptor has the venus flytrap extracellular domain?

mGluRs

29

What percent of inhibitory synaptic activity is mediated by GABA? What percent of neurons is it in?

40%

And it is present in 20% of neurons

30

What inhibitory NT can also be found in the pancreas?

GABA

31

What receptor needs co-activation by both glutamine and glycine?

NMDA receptor

32

What do GABAb receptors do upon binding with GABA? (3)

- Inhibit cAMP
- Increase K+ conductance
- Decreases calcium ion conductance

33

Mice lacking the γ2 subunit of GABAa show?

Death shortly after birth, due to lack of receptor clustering.

Heterozygous mice don't die, but act as a model for anxiety (heightened fear response)

34

What drugs have relaxing, anti-anxiety and anti-convulsive effects and are commonly used to treat insomnia?

GABAa agonists

35

What is GHB?

γ-hydroxybutyric acid

- A weak agonist of GABAb receptors and the novel GHB receptor

36

What are the genes involved in hyperekplexia? (2)

The complete loss of which of these genes is lethal?

- GLRA1 (alpha-1 subunit for glycine receptor)
- GLRB (beta subunit for glycine receptor)

Loss of expression of either of these can lead to startle disease. Complete loss of GLRA1 is lethal

37

What is strychnine and what does doses of it cause?

Glycine antagonist

- A low dose causes hyperekplexia and increase in muscle tone
- A high dose causes convulsions and death

38

What opioid enhances function of glycine receptors?

Cannabinoids

39

The loss of what receptors results in resistance to cannabinoid-induced analgesia?

α3GlyRs (alpha-3 glycine receptors)

Not in those lacking cannabinoid-1 or 2 receptors. (shows that cannabinoids can have an effect on glycine receptors and the brain even when cannabinoid receptors are absent)

40

What are the five types of adrenergic (catecholamine receptors - eg. norepinephrine)? What G-proteins are they linked to?

α1: Gq
α2: Gi

β1,2,3: Gs

41

Which type of adrenergic receptor is located presynaptically? Why?

α2

To control norepinephrine release

42

What type of adrenergic receptor has a negative feedback loop? How does it work?

β-adrenergic receptors

1. GRK phosphorylates the receptor
2. β-arrestin promotes receptor internalization by binding to clathrin
3. Clathrin promotes endocytosis
4. Internalized receptors can be recycled or degraded

43

Which dopamine receptor knockouts result in supersensitivity or reduced locomotion to cocaine and amphetamines? (3)

- D3 (supersensitivity)
- D4 (supersensitivity)
- D1 (reduction in activity)

44

What dopamine receptors might play a role in hypertension? (3)

- D1
- D3
- D5

45

What are neuroleptics?
What is a benefit and a side effect?

- D2-like receptor antagonists

These can control psychosis

Often induce Parkinson's like effects by acting on nigrostriatal pathway

46

What is another name for L-aromatic amino acid decarboxylase? What are the two most common reactions for this enzyme in the brain?

DOPA-decarboxylase

- Synthesizes 5-HT from 5-HTP
- Synthesizes dopamine from L-DOPA

47

Presynaptic serotonin receptors can do two different things, what are the two receptors?

- 5-HT autoreceptors (IE. 5-HT1B) can Inhibit the release of neurotransmitter
- 5-HT3 can facilitate the release of NTs

48

Which serotonin receptor binding is decreased in patients with depression?

5-HT1A

49

LSD and other hallucinogens active what receptors?

5-HT2A

50

What serotonin receptor knockout may cause obesity, convulsions and cognitive impairment?

5-HT2C

51

A point mutation in what cleavage site of proopiomelanocortin leads to what?

- Between β-melanotrophins (β-MSH) and β-endorphins
- Leads to aberrant peptide synthesis, which causes obesity in humans by altering central melanocortin signalling in the CNS.

52

What is an example of neuropeptides which are co-stored and co-released and exerting opposing actions?

Dynorphin and hypocretin (orexin)

53

What is NKA and NKB?

Neurokinin A and B, bind to tachykinin receptors to mediate pain.

54

Galanin knockout shows?

Increased anxiety

55

What competes with NOS (nitric oxide synthase)?

Arginases, which are induced by cytokines

56

How can nitroglycerin prevent acute chest pain?

It is a substrate of NO, which can induce vasodilation of cardiac blood vessels.

57

True or false? The four P1 adenosine receptors (A1, A2a, A2b and A3) are metabotropic

True!

58

Which adenosine receptors (P1) are coupled with Gs? Which are coupled with Gi/o?

Gs: A2a, A2b

Gi/o: A1, A3

59

What ions are allowed to flow through P2X receptors?

Calcium and sodium

60

Activation of microglia by ATP is known to be involved in?

Neuropathic pain

61

What two neurotransmitters promote myelination by oligodendrocytes?

ATP and adenosine

62

Stimulation of the P2X7 receptors on oligodendrocytes mediates ___, while adenosine ___ them through the P1 receptor.

Stimulation of the P2X7 receptors on oligodendrocytes mediates apoptosis, while adenosine protects them through the P1 receptor.

63

What are three ways purinergic receptors modulate vasodilation and vasoconstriction?

Purinergic receptors on perivascular nerves

- Norepinephrine and ATP can stimulate P2X receptors to produce vasoconstriction

- Endothelium and platelet derived ATP and ADP stimulated both P2Y and P2X to induce NOS to synthesize epithelium-derived relaxing factor (Nitric oxide), leading to vasodilation

- ATP derived adenosine (ADO) acts on P1 receptors to induce vasodilation

64

What type of drug is used to inhibit blood clots in artery disease? How?

PTY antagonist

65

Slow neurotransmitters are mostly taken up by ___?

Transported back to pre-synaptic terminal in the perisynaptic region

66

Fast neurotransmitters are mostly taken up by ___?

Glia

67

What is the RACK1?

Receptor for activated C kinase, which binds to the N terminus of DAT and plays an important role as PKC substrate

68

What does DAT-protein phosphatase 2 (PP2A) do?

Interacts with DAT N terminus to induce downregulation of DAT

69

What does ubiquitin do with DAT?

ubiquitin-protein ligase NEDD4 triggers PKC-mediated DAT internalization

70

How many peopel does depression affect worldwide?

120 million people

71

In addition to SERT-selective inhibitors, what aer two other inhibitors used to treat depression?

- NET/SERT inhibitors
- NET selective inhibitors

72

How many GATs are there and where are they found around synapses (2)?

3 GAT1-3

FOund on presynaptic terminals and on glia

73

Which GLYT knockout results in hyperexplexia?

GLYT2

74

Which GLYT is found on glia?

GLYT1

Also inhibited by N-methyglycine

75

What are the 6 EAATs and where are they found?

- EAAT1 (astrocytes and oligodendrocytes)
- EAAT2 (astrocytes and oligodendrocytes)
- EAAT2b (astrocytes and neurons)
- EAAT3 (neurons)
- EAAT4 (purkinje cells)
- EAAT5 (photoreceptors and bipolar cells in the retina)

76

How is glutamate taken into neurons?

As glutamine, must be converted to glutamate by glutaminase in the soma

77

What transporter is involved in alcoholism?

Equilibrative nucleoside transporter 1 (ENT1)

Knockout show increased alcohol consumption and reduced EAAT2 levels in the striatum

78

What is the basic mechanism for ABC transport?

- Dimers across membrane
- Allosteric ligand binding on the 'intracellular' side induces conformational change and increased affinity for ATP
- Ligand secreted with hydrolysis of ATP
- Pi and ADP released

This mechanism acts to pump materials out of cells

79

What is a positive marker?

Positive selectable markers are selectable markers that confer selective advantage to the host organism.[5] An example would be antibiotic resistance, which allows the host organism to survive antibiotic selection.

80

What is a negative marker?

Negative selectable markers are selectable markers that eliminate or inhibit growth of the host organism upon selection.[6] An example would be thymidine kinase, which makes the host sensitive to ganciclovir selection.

81

What is the function of a negative marker with transgene insertion using recombination?

With homologous recombination the negative selection marker will not be included but the DNA construct will.

In non-homologous recombination the DNA construct and the negative selection marker are both included. The selection marker (usually thymidine kinase gene) will kill these cells so that only homologous recombinants and non recombinants are present.

Positive selection markers (eg. reporter genes) can then be used to isolate homologous recombinants