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Neuropharmacology > Exam 2 Material > Flashcards

Exam 2 Material Flashcards

1
Q

What are the two types of glutamate transporters?

A

1 vesicular transporters

2 membrane transporters

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2
Q

Name a vesicular glutamate transporter

A

VGluT1-3

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3
Q

What does VGluT1-3 have a high/low affinity for?

A

glutamate, aspartate

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4
Q

What does VGluT1-3 do?

A

it sits on the vesicle and pumps glutamate into it

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5
Q

What are the two glial membrane glutamate transporters?

A

GLAST (glutamate aspartate transporter) and GLT-1 (glutamate transporter 1)

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6
Q

What function do the glutamate membrane transporters serve?

A

they help with buffering so you can turn signaling off

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7
Q

How do glia play a role in signal spread?

A

They can engulf multiple synapses which leads to signals spreading via them

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8
Q

If you wanted to create a drug to treat a disease where glutamate levels were undetectable, what methods/drugs could you use?

A

???

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9
Q

Who coined the phrase excitotocity?

A

John Olney in his study on MSG

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10
Q

The damage that John Olney found can happen with what kind of drugs in relation to glutamate?

A

antagonists

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11
Q

What are calcium buffers in the cell?

A

ER and mitochondria

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12
Q

Define auto-receptor:

A

s a type of receptor located in the membranes of presynaptic nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the autoreceptor sits.

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13
Q

Metabotropic glutamate receptors have ___ transmembrane domains with the agonist binding site located on the __ _____.

A

seven, N terminus

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14
Q

Presynaptic mGluRs act as _____ _____ by reducing _____ influx.

A

inhibitory autoreceptors, Ca 2+ influx

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15
Q

What famil(y/ies) include presynaptic mGluRs?

A

mGluRII and III

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16
Q

How do presynaptic mGluRs act on the cell?

A

By reducing Ca2+ influx

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17
Q

What do postsynaptic mGluRs do?

A

they modulate a variety of ligan and voltage gated ion channels

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18
Q

What famil(y/ies) include postsynaptic mGluRs?

A

mGluRs I

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19
Q

What is the homer binding site involved in?

A

clustering of receptors

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20
Q

What undergoes extensive splice variation?

A

the C terminus

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21
Q

what is a homer protein?

A

an anchoring protein

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22
Q

What is responsible for specificity with mGluRs?

A

the 2nd intracellular loop and C terminal domain

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23
Q

What type of receptor is LTP dependent on?

A

NMDAR

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24
Q

What type of receptor is LTD dependent on?

A

NMDAR and mGluR

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25
Q

What modulates CamKII?

A

Ca 2+

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26
Q

What does CamKII do?

A

phosphorylates

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27
Q

What does calcineurin do?

A

dephosphorylates

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28
Q

Where are the receptors that work on LTP found?

A

at the synapse

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29
Q

Where are the receptors that work on LTD found?

A

for NMDAR: synapse

for mGluR: extrasynaptic

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30
Q

What is the result of LTP?

A

postsynaptic insertion AMPARs

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31
Q

What is the result of LTD?

A

internalization of postsynaptic AMPARs

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32
Q

What diseases are related the mGluR- LTD?

A

Alzheimer’s, Fragile X, Parkinson’s, concaine self administration, drug addiction

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33
Q

What is a coagonist of NMDA channels?

A

serine

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34
Q

What is an example of a positive modulator of AMPA channels?

A

pircetam (nootropics)

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35
Q

B6—> ____ —> cofactor to make GABA

A

pyridoxal phosphate

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36
Q

_____ requires cofactor of pyridoxal phosphate.

A

GAD (glutamic acid decarboxylase)

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37
Q

What is derived from vitamin B6?

A

pyridoxal phosphate.

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38
Q

What does lack of B6 do to the brain?

A

reduces GABA content which can cause seizures

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39
Q

GABA and glycine are ______ transmitters.

A

inhibitory

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40
Q

Where is GABA found?

A

throughout the CNS

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41
Q

Where is glycine found?

A

mostly in the brainstem and spinal cord

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42
Q

What components make GABA?

A

glutamate with p. phosphate

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43
Q

What functions are glycine important to?

A

spinal reflexes

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44
Q

What are the ligand-gated ion channels for GABA?

A

GABA A and GABA C

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45
Q

Where is GABA C found?

A

almost primarily in the retina

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46
Q

What GABA is a GPCR?

A

GABA B

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47
Q

What are GABA ion channels selective for?

A

Cl- and HCO3_

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48
Q

What effect do GABA ion channels have on the cell?

A

they are inhibitory- have a hyperpolarizing effect (because of the Cl- entering)

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49
Q

What subunits are typical to GABA receptors?

A

alpha and beta almost always with additions of gamma, delta, pi and epsilon to attach to those

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50
Q

What are some agnosits of GABA A receptors?

A

GABA and muscimol

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51
Q

What are some antagonists to GABA A receptors?

A

bicuculline, flumazenil, picrotoxin

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52
Q

What are 3 of the 5 classes of positive allosteric modulators for GABA A receptors?

A
  1. benzodiazepines
  2. non benzos that bind at benzo site
  3. barbiturates
  4. anesthetics
  5. ethanol
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53
Q

What is a negative allosteric modulator of GABA A?

A

prenenolone (a neurosteroid)

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54
Q

How do GABA A allosteric modulators work?

A

they only modulate (do not work on their own!) by quieting down the neurons

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55
Q

What must you have to open a GABA A channel?

A

an agonist

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56
Q

What is the benzo mediated effect of an alpha 1 unit?

A

sedative, antero amnesia, and aticonvulsant (think ambien walrus on the ground flopping in his sleep)

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57
Q

What is the benzo mediated effect of an alpha 2 unit?

A

anxiolytic and muscle relaxant

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58
Q

What is the benzo mediated effect of an alpha 3 unit?

A

anxiolytic and muscle relaxant

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59
Q

What is the benzo mediated effect of an alpha 5 unit?

A

cognitive effects

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60
Q

What alpha units do you want an anxiety drug to bind to on the alpha subunit?

A

2 and 3 and NOT 1

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61
Q

What alpha units do you want a sedative drug to bind to on the alpha subunit?

A

1 and NOT 5

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62
Q

What effect do glycine receptors have on neurons?

A

they are hyperpolarizing and inhibitory

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63
Q

What subunits do glycine receptors use?

A

same as GABA- alpha and beta

64
Q

What are some glycine agonists?

A

glycine, beta or l alanine, taurine, L-serine, proline (all amino acids)

65
Q

What are positive allosteric modulators of glycine?

A

anesthetics, neurosteroids, and ethanol

66
Q

What is a negative allosteric modulator of glycine?

A

pregnenolone

67
Q

What is an antagonist of glycine?

A

strychnine

68
Q

Which GABA transporters have a high affinity for GABA?

A

GAT-1, GAT-2, GAT-3

69
Q

Which GABA transporters have a low affinity for GABA?

A

BGT-1

70
Q

Which things block GABA transporters?

A

taurine, hypotaurine, L-DABA, B-alanine, tiagabine, guvacine

71
Q

What does glycine do on NMDA channels?

A

it is a coagnost for it

72
Q

Where are glycine channels at?

A

mostly in the spine

73
Q

What is the transporter for glycine in neurons and astrocytes?

A

GLYT1

74
Q

What is the transporter for glycine in neurons?

A

GLYT2

75
Q

What blocks GLYT1?

A

sarcosine

76
Q

What is a GABA B receptor agonist?

A

baclofen (potent!)

77
Q

What are GABA B antagonists?

A

saclofen, phaclofen

78
Q

What is a signaling mechanism GABA B receports use?

A

they dimerize

79
Q

What are GABA B receports good for?

A

slower but longer lasting inhbibtion

80
Q

Where are GABA B receptors in the cell?

A

pre and postsynaptic- they are Gi/o coupled

81
Q

What kind of stimuli do extrasynaptic GABA B receports need?

A

longer duration and higher frequency

82
Q

What is the synaptic function of a GABA B heteroreceptor?

A

it inhibits GABA on glutaminergic neurons

83
Q

What is the synaptic function of a GABA B autoreceptor?

A

they inhibit on GABA neurons

84
Q

GABA B receports inhibit pre-synaptic ____ channels and ____ _____ resulting in ______ transmitter release.

A

Ca2+, adenylyl cyclase, decreased

85
Q

What is PSD?

A

post-synaptic density; a collection of proteins that recruit and anchor receports and signaling molecules

86
Q

What is a common example of a molecule that contributes to formation of correct synapses?

A

neurexin/neurolignan

87
Q

how do pre and post synaptic cells line up so that they communicate effectively?

A

they have the same receptor and NT

88
Q

Extracellular pairing is an example of interaction that helps direct _____ ______.

A

Synaptic interactions

89
Q

What is the job of beta-neurexin?

A

it aligns vesicles

90
Q

What is the job of neurlignan?

A

it anchors

91
Q

What are peptides?

A

polymers of amino acids linked together by amine bonds

92
Q

What are neuropeptides?

A

specific peptides that act as neurotransmitters in the nervous system

93
Q

What signals an N terminus?

A

an NH2

94
Q

What is an N terminus?

A

the start of a protein or polypeptide terminated by an amino acid with a free amine group (-NH2)

95
Q

What signals a C terminus?

A

-COOH

96
Q

What is an C terminus?

A

he end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH)

97
Q

How many main amino acids are there?

A

20

98
Q

How many essential amino acids are there?

A

8

99
Q

What is an amino acid?

A

a simple organic compound containing both a carboxyl (—COOH) and an amino (—NH2) group and it has an R side group

100
Q

What is a neuropeptide?

A

small protein-like molecules (peptides) used by neurons to communicate with each other

101
Q

What is the secondary structure of an amino acid?

A

a helix or beta pleated sheets

102
Q

Neuropeptides produce neuronal responses with _____ onset and ____ duration.

A

slow, long

103
Q

Neuropeptides serve what function in the cell?

A

modulators

104
Q

Are ion channels directly opened by neuropeptides in mammals?

A

no

105
Q

Neuropeptide recovery does not depend on ______ ________.

A

reuptake transporters

106
Q

What is required for recovery for neuropeptides?

A

1- RNA transcription
2- protein translation
3- axonal transport

107
Q

What neuropeptide has the opposing functions to opioids?

A

CCK, cholecystokinin

108
Q

What does CCK do in the periphery?

A

stimulates digestion of fat and protein

109
Q

What does CCk do in neural areas?

A

it induces anxiety and nausea

110
Q

What does angiotensin do in the periphery?

A

it causes vasoconstriction

111
Q

What does angiotensin do in neural areas?

A

thirst

112
Q

What does oxytocin do in the periphery?

A

lactation, uterine contractions during labor

113
Q

What does oxytocin do in neural areas?

A

anti-stress, maternal behavior, pain reduction

114
Q

What are the four major functions of neuropeptides?

A

1- modulation of sensory information
2- modulation of emotion
3- learning and memory
4- feeding and energy balance

115
Q

What does Substance P do?

A

enhances pain perception

116
Q

What does calcitonin gene-related peptide do? (CGRP)

A

plays a role in migraines

117
Q

What are enkephalins associated with?

A

reduced pain perception

118
Q

What does CRF (corticotrophin releasing factor) play a role in?

A

fear and anxiety

119
Q

What does vasopressin do?

A

plays a role in memory formation

120
Q

What role do opioids play in memory?

A

they are thought to play a role in memory loss

121
Q

What has NPY been linked to?

A

food intake and obesity

122
Q

Where is norepinephrine produced?

A

pons and medulla

123
Q

What structure contains over 50% of the NE neurons in the brain?

A

locus ceruleus (LC) in the pons

124
Q

What does NE signaling contribute to?

A

sleep-wake cycle (arousal), attention, anxiety

125
Q

What are NE modulating drugs used in the treatment of?

A

ADHD

126
Q

NE acting on beta receptors in the amygdala ______ memory for negative emotions.

A

increases

127
Q

What is the rate-limiting enzyme for NE creation?

A

tyrosine hydroxylase (TH)

128
Q

TH is thought to be _____ under normal conditions.

A

saturated

129
Q

What is TH inhibited by?

A

catecholamines (feedback inhibition)

130
Q

What is required as a cofactor for HT?

A

BH4 (tetrahydrobiopterin)

131
Q

What does AADC rquire as a cofactor?

A

pyroxidal-5-phosphate (derivative of B6)

132
Q

Tyrosine is acted on by TH to make _____ which is acted on by L-AADC to make ______ which is acted on by DBH to make ______ which is acted on by phenylethanoamine N methyltransferase to make _______.

A

L-Dopa
Dopamine
Noradrenaline
Adrenaline

133
Q

List the order of biosynthesis of adrenaline (only the created molecules). 5 steps

A 
1- tyrosine
2- L Dopa
3- Dopamine
4- Noradrenaline (norepi)
5- Adrenaline (epi)
134
Q

What are the four molecules that act on molecules to aid in biosynthesis of adrenaline.

A

1- TH (tyrosine hydroxylase)
2- L-AADC (L Aromatic amino acid)
3- DBH (dopamine beta hydroxylase)
4- phenylethanoamine N-methyltransferase

135
Q

What are the steps of synthesis of serotonin? 3 molecules

A

1- tryptophan
2- 5 HTP
3- 5 HT (serotonin)

136
Q

What does serotonin lead to synthesis of?

A

melatonin

137
Q

What molecule acts on tryptophan to lead to synthesis of 5 htp?

A

tryptophan hydroxylase

138
Q

What molecule acts of 5 HTP to lead to synthesis of 5 HT (aka serotonin)?

A

L-AADC

139
Q

What two things degrade catecholamines?

A

MAO or COMT

140
Q

MAO A is mostly in _______ neurons and metabolizes 5HT, ____, epi, ____ and tyramine.

A

norandrenergic neurons, NE, DA

141
Q

MAO B is mostly in _______ and ________ neurons and metabolizes DA.

A

serotonergic and histaminergic

142
Q

What do MAO inhibitors inhibit the breakdown of?

A

catecholamines

143
Q

What are some examples of MAOIs?

A

isocarboxazid, phenelzine, tranylcypromine, selegiline

144
Q

What does VMAT transport?

A

monoamines (multiple)

145
Q

Is VMAT selective?

A

no

146
Q

What are the two isoforms of VMAT?

A

VMAT1 and VMAT2

147
Q

What is VMAT inhibited by?

A

reserpine and terabenazine

148
Q

How does guanethidine interact with NET?

A

it is taken up by it then concentrated in vesicles; it will eventually deplete the vesicles of NE

149
Q

What does dopamine degrade into via MAO?

A

homovanillic acid

150
Q

What does norepinephrine degrade into via MAO?

A

vanillylmandelic acid or MHPG

151
Q

How are catecholamines regulated?

A

1- diffusion away from synapses
2- metabolic breakdown
3- reuptake into nerve terminals

152
Q

how many transmembrane domains does NET have?

A

12

153
Q

How does cocaine impact catecholamines?

A

it inhibits reuptake of NE, epi, and DA by blocking NET/DAT

154
Q

How does Ritalin act on the brain?

A

it blocks NET/DAT but probably does not increase NET/DA release

155
Q

How does amphetamine act on NE/DA?

A

it inhibits reuptake via competition and depletes NE/DA from vesicles via disruption to the proton gradient

156
Q

How does amphetamine stimulate the efflux of NE/DA?

A

it phosphorylates NET/DAT

Neuropharmacology (3 decks)

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