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physiology and pharma > L1 - NT systems > Flashcards

L1 - NT systems Flashcards

1
Q

where is ACh found in CNS

A
  1. interneurones of the striatum
  2. nucleus basalis pathways
  3. septohippocampal pathway
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2
Q

where is ACh found in periphery

A 
lower motor neuornes
GI tract 
all preganglionic SNS nerves 
all PNS nerves 
retina
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3
Q

where does ACh synthesis occur

A

cytoplasm of nerve terminal

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4
Q

describe synthesis of ACh

A

choline + acetyl CoA -> ACh

(via choline acetyltransferase

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5
Q

where is choline acetyltransferase synthesised? (ChAT)

A

cell body, then transported to nerve termminals

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6
Q

where does choline come from for ACh synthesis?

where does Acetyl CoA come from for ACh synthesis?

A

diet or recycled from breakdown of ACh

krebs cycle

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7
Q

describe storage of ACh

A

VAChT (vesicular ACh Transporter) antiports 1x ACh+ into the vesicle and 2xH+ out of the vesicle

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8
Q

what is the [ACh] inside the vesicle and in cytoplasm

A

inside 1000mM

cytoplasm 1mM

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9
Q

is ACh release Ca dependant?

A

yes

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10
Q

what are the 3 types of vesicle pools? and describe them

A

releasable -> fused to membrane and ready to release NT
recyclable -> returning to collect NT, transporters and synaptobrevin being re-added to mmebrane
reserve -> not in use

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11
Q

briefly describe what type of receptor the nicotinic ACh receptor is
- how many subunits

A

ligand gated ion channel

5 (pentameric)

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12
Q

where are NAChRs found?

A

muscle
embryonic muscle
ganglion
CNS

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13
Q

what type of NAChRs are found in ganglion?

A

alpha 3 and beta 4

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14
Q

what NAChRs are found in CNS

A

a4 , a7 , B2

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15
Q

what type of receptors are the MAChRs

A

GPCRs (class A,, rhodopsin like)

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16
Q

what G protein is coupled to M1 receptors

A

Gq/G11

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17
Q

what G protein is coupled to M2 receptors

A

Gi/Go

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18
Q

what G protein is coupled to M3 receptors

A

Gq/G11

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19
Q

what G protein is coupled to M4 receptors

A

Gi/Go

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20
Q

what G protein is coupled to M5 receptors

A

Gq/G11

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21
Q

where is ACh degraded?

A

in the synaptic cleft

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22
Q

describe breakdown of ACh

A

ACh -> choline + acetic acid

Via acetylcholinesterase

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23
Q

describe ACh reuptake process

A

once broken down to choline, the choline transporter transports choline back into presynaptic terminal (recycling)

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24
Q

name agonists of nAChRs

A

suxamethonium

nicotine

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25
Q

name antagonist of nAChR

A

pancronium

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26
Q

name agonist of mAChR

A

muscarine

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27
Q

function of hemicholinium?

A

blocks reuptake of choline

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28
Q

name a drug that blocks ACh degradation

A

rivastigmine

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29
Q

list some diseases involving ACh

A 
parkinsons (motor control)
myasthenia gravis (NMJ)
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30
Q

what type of NT is dopamine

A

monoamine

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31
Q

where is DA founnd in CNS?

A

nigrostriatal pathway
mesolimbic and mesocorticol pathway
tubero-hypophyseal pathway

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32
Q

where is DA found in the periphery

A

retina

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33
Q

where does DA synthesis occur

A

cytoplasm of nerve terminal

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34
Q

describe process of DA synthesis

A

tyrosine -> DOPA (via tyrosine hydroxylase)

DOPA -> dopamine (via dopadecarboxylase)

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35
Q

what is the rate limiting step in DA synthesis

A

tyrosine -> dopa via tyrosine hydroxylase

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36
Q

where can we get tyrosine from

A

diet

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37
Q

what is the name of the transporter that transports DA into vesicle

A

VMAT (1 or 2) vesicular monoamine transporter

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38
Q

describe locations of VMAT 1&2

A

vesicular membrane

cell specific, certain cells contain each one

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39
Q

describe storage of DA

A

VMAT1/2 transport DA + in turn for 2x H+

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40
Q

how is high [H+] maintained within vesicles?

A

ATPase pump

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41
Q

is DA release Ca dependant

A

yes

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42
Q

describe release of DA (not process)

A

released from terminal and en passant variscosities

DA released all the way along the axon

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43
Q

what are en passant variscosities

A

regions along the axon that can release NT (not the terminal)

44
Q

list NTs that are released from en passant variscosites aswell as the terminal

A

DA

NA

45
Q

what type of receptors are DA receptors

A

GPCRs (class A, rhodopsin like)

46
Q

how many subtypes of DA are there and what are they

A

5
D1 like -> excitatory
D2 like -> inhibitory

47
Q

what are D1 -like receptors coupled to

A

Gs

48
Q

what DA receptors are considered D1 like?

A

D1, D5

49
Q

what DA receptors are considered D2-like

A

D2 D3 D4

50
Q

what are D2 like receptors coupled to

A

Go/Gi

51
Q

describe re-uptake of DA

A

reuptake via co-transporter DAT (dopamine active transporter) along with Cl- and 2Na

52
Q

what is the end product for the breakdown of DA

A

homovanillic acid

53
Q

name a drug that can block stroage of DA

A

reserpine

54
Q

agonists of DA

A

apomorphine

55
Q

antagonist of DA

A

chlopromazine

56
Q

what effect does cocaine have on DA?

A

blocks reuptake of DA

57
Q

what drug classes can block DA degradation (give examples)

A 
MAO inhibitors (selegiline) 
COMT inhibitors (entacapone
58
Q

what is COMT

A

Catechol - O - methyltransferase

59
Q

list some diseaeses involving DA

A

parkinsons
drug dependance (reward process)
schizophrenia (thought)

60
Q

what enzymes degrade DA

A

MAO monoamine oxidase

COMT - Catechol - O - methyltransferase

61
Q

what NTs are monoamines

A

DA

NA

62
Q

where is NA found in brain

A

many locations, including

  • cerebellum
  • brainstem and spinal cord
  • amigdyla
  • hypothalamus
  • substantia nigra
  • locus coeruleus
63
Q

where is NA found in periphery

A

postganglionic SNS nerves

retina

64
Q

describe synthesis of NA

A

tyrosine -> DOPA (tyrosine hydroxylase)
DOPA -> DA (dopa decarboxylase)
DA -> NA (dopamine B hydroxylase)

65
Q

where is dopamine B hydroxylase found

A

only in the vesicles of noradrenergic neurones

66
Q

where is NA synthesised

A

DA is synthesised in cytoplasm then is converted to NA in the vesicle

67
Q

describe NA storage

A

same as DA, via VMAT1/2 in exchange for 2H+

68
Q

describe release of NA

A

Ca dependant
released from terminals and en passant variscosities
often co released with ATP

69
Q

what is NA often co released with?

A

ATP

70
Q

what type of receptors are NA receptors

A

GPCRs (class A, rhodopsin like)

71
Q

what are a1 NA receptors coupled to

A

Gq/G11

72
Q

what are a2 NA receptors coupled to

A

Gi/Go

73
Q

are a1 pre or post synaptic

A

post

74
Q

does adrenaline or NA have higher affinity for a1 receptors

A

NA

75
Q

are a2 NA receptors pre or post synaptic

A

presynaptic

76
Q

does adrenaline or NA have higher affinity for a2 receptors

A

adrenaline

77
Q

what are B1, B2 and B3 NA receptors coupled to?

A

Gs

78
Q

do B1
B2
B3
NA receptors have higher affinity for NA or adrenaline

A
  • ß1 - NA > Ad
  • ß2 - Ad > NA
  • ß3 - NA = Ad
79
Q

describe re uptake of NA

A

Uptake 1 - back into neurone via NET (norepinephrine co-transporter)

Uptake 2 - into glial cells (astrocytes) via NET

80
Q

describe the NA re-uptake transporter

A

NET - norepinephrine transporter

co transports NA along with Cl- and Na+ into the terminal or astrocytes

81
Q

what uptake method for NA is into astrocytes?

A

uptake 2

82
Q

what is the final product in the breakdown of NA

A

VMA -> vanillylmandelic acid

83
Q

where is NA excreted?

A

in the urine as vanillylmandelic acid

84
Q

what enzymes breakdown NA

A

MAO

COMT ( catechol - O - methyltrannsferase

85
Q

name a a1 agonist of NA

A

clonidine

86
Q

name a B2 NA agonist

A

salbutamol

87
Q

name a B NA antagonist

A

propranalol

88
Q

name a a1 NA antagonist

A

prazosin

89
Q

name drug classes that block NA reuptake and give example

A

NSRI (NA selective re-uptake inhibitors) - reboxitine
TCAs (imipramine)
cocaine
amphetamine

90
Q

list diseases NA is involved in

A

hypertension (SNS, CV control)

91
Q

what type of NT is 5-HT

A

indolamine

92
Q

where is 5-HT found in brain

A 
hippocampus & amygdala 
raphe nuclei 
cerebellum 
hyppothalamus & thalamus & striatum 
Substantia nigra
93
Q

where is 5-HT located in the periphery

A

enteric nervous system
retina
platelets

94
Q

where is serotonin synthesised

A

cytoplasm of nerve terminal

95
Q

describe synthesis of serotonin

A

tryptophan -> 5-hydroxytryptophan ( tryptophan hydroxylase)

5-hydroxytryptophan -> 5-hydroxytryptamine (dopa decarboxylase

96
Q

what does 5-HT stand for

A

serotonin

5-hydroxytryptamine

97
Q

is serotonin released from en passant variscosities?

A

no

98
Q

can serotonin be co released?

A

yes, with somatostatin / substance P

99
Q

what type of receptor is the 5-HT3 receptor

A

ligand gated ion channel (mixed cation)

100
Q

what serotonin receptor subtypes are coupled to Gs?

A

5HT-4
5-HT6
5-HT7

101
Q

what serotonin receptor subtype is found presynaptically and what does it couple to?

A

5-HT1

Gi/Go

102
Q

what does 5-HT2 receptor couple to?

A

Gq/G11

103
Q

describe re-uptake of 5-HT

A

SERT (serotonin reuptake transporter) co transports 5-HT into terminal along with Cl- and 2Na+

104
Q

describe degradation of 5-HT

A

5-HT -> 5-hydroxyindolealdehyde (via monoamine oxidase)

5-hydroxyindolealdehyde -> 5-hydroxyindoleacetic acid 5-HIAA (via aldehyde dehydrogenase)

105
Q

5-HT3 antagonist

A

ondansetron

106
Q

name drug classes that block the re-uptake of 5-HT and give examples

A

SSRIs (citalopram)
TCAs (imipramine)
Amphetamine

107
Q

list other NTs (9)

A 
bradykinin 
ATP 
substance P 
glycine 
Glutamate 
NO 
histamine 
GABA 
neuropeptide Y

physiology and pharma (18 decks)

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