Exam 2 Material Flashcards
(156 cards)
1
Q
What are the two types of glutamate transporters?
A
1 vesicular transporters
2 membrane transporters
2
Q
Name a vesicular glutamate transporter
A
VGluT1-3
3
Q
What does VGluT1-3 have a high/low affinity for?
A
glutamate, aspartate
4
Q
What does VGluT1-3 do?
A
it sits on the vesicle and pumps glutamate into it
5
Q
What are the two glial membrane glutamate transporters?
A
GLAST (glutamate aspartate transporter) and GLT-1 (glutamate transporter 1)
6
Q
What function do the glutamate membrane transporters serve?
A
they help with buffering so you can turn signaling off
7
Q
How do glia play a role in signal spread?
A
They can engulf multiple synapses which leads to signals spreading via them
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
???
9
Q
Who coined the phrase excitotocity?
A
John Olney in his study on MSG
10
Q
The damage that John Olney found can happen with what kind of drugs in relation to glutamate?
A
antagonists
11
Q
What are calcium buffers in the cell?
A
ER and mitochondria
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.
13
Q
Metabotropic glutamate receptors have ___ transmembrane domains with the agonist binding site located on the __ _____.
A
seven, N terminus
14
Q
Presynaptic mGluRs act as _____ _____ by reducing _____ influx.
A
inhibitory autoreceptors, Ca 2+ influx
15
Q
What famil(y/ies) include presynaptic mGluRs?
A
mGluRII and III
16
Q
How do presynaptic mGluRs act on the cell?
A
By reducing Ca2+ influx
17
Q
What do postsynaptic mGluRs do?
A
they modulate a variety of ligan and voltage gated ion channels
18
Q
What famil(y/ies) include postsynaptic mGluRs?
A
mGluRs I
19
Q
What is the homer binding site involved in?
A
clustering of receptors
20
Q
What undergoes extensive splice variation?
A
the C terminus
21
Q
what is a homer protein?
A
an anchoring protein
22
Q
What is responsible for specificity with mGluRs?
A
the 2nd intracellular loop and C terminal domain
23
Q
What type of receptor is LTP dependent on?
A
NMDAR
24
Q
What type of receptor is LTD dependent on?
A
NMDAR and mGluR
25
What modulates CamKII?
Ca 2+
26
What does CamKII do?
phosphorylates
27
What does calcineurin do?
dephosphorylates
28
Where are the receptors that work on LTP found?
at the synapse
29
Where are the receptors that work on LTD found?
for NMDAR: synapse
| for mGluR: extrasynaptic
30
What is the result of LTP?
postsynaptic insertion AMPARs
31
What is the result of LTD?
internalization of postsynaptic AMPARs
32
What diseases are related the mGluR- LTD?
Alzheimer's, Fragile X, Parkinson's, concaine self administration, drug addiction
33
What is a coagonist of NMDA channels?
serine
34
What is an example of a positive modulator of AMPA channels?
pircetam (nootropics)
35
B6---> ____ ---> cofactor to make GABA
pyridoxal phosphate
36
_____ requires cofactor of pyridoxal phosphate.
GAD (glutamic acid decarboxylase)
37
What is derived from vitamin B6?
pyridoxal phosphate.
38
What does lack of B6 do to the brain?
reduces GABA content which can cause seizures
39
GABA and glycine are ______ transmitters.
inhibitory
40
Where is GABA found?
throughout the CNS
41
Where is glycine found?
mostly in the brainstem and spinal cord
42
What components make GABA?
glutamate with p. phosphate
43
What functions are glycine important to?
spinal reflexes
44
What are the ligand-gated ion channels for GABA?
GABA A and GABA C
45
Where is GABA C found?
almost primarily in the retina
46
What GABA is a GPCR?
GABA B
47
What are GABA ion channels selective for?
Cl- and HCO3_
48
What effect do GABA ion channels have on the cell?
they are inhibitory- have a hyperpolarizing effect (because of the Cl- entering)
49
What subunits are typical to GABA receptors?
alpha and beta almost always with additions of gamma, delta, pi and epsilon to attach to those
50
What are some agnosits of GABA A receptors?
GABA and muscimol
51
What are some antagonists to GABA A receptors?
bicuculline, flumazenil, picrotoxin
52
What are 3 of the 5 classes of positive allosteric modulators for GABA A receptors?
1. benzodiazepines
2. non benzos that bind at benzo site
3. barbiturates
4. anesthetics
5. ethanol
53
What is a negative allosteric modulator of GABA A?
prenenolone (a neurosteroid)
54
How do GABA A allosteric modulators work?
they only modulate (do not work on their own!) by quieting down the neurons
55
What must you have to open a GABA A channel?
an agonist
56
What is the benzo mediated effect of an alpha 1 unit?
sedative, antero amnesia, and aticonvulsant (think ambien walrus on the ground flopping in his sleep)
57
What is the benzo mediated effect of an alpha 2 unit?
anxiolytic and muscle relaxant
58
What is the benzo mediated effect of an alpha 3 unit?
anxiolytic and muscle relaxant
59
What is the benzo mediated effect of an alpha 5 unit?
cognitive effects
60
What alpha units do you want an anxiety drug to bind to on the alpha subunit?
2 and 3 and NOT 1
61
What alpha units do you want a sedative drug to bind to on the alpha subunit?
1 and NOT 5
62
What effect do glycine receptors have on neurons?
they are hyperpolarizing and inhibitory
63
What subunits do glycine receptors use?
same as GABA- alpha and beta
64
What are some glycine agonists?
glycine, beta or l alanine, taurine, L-serine, proline (all amino acids)
65
What are positive allosteric modulators of glycine?
anesthetics, neurosteroids, and ethanol
66
What is a negative allosteric modulator of glycine?
pregnenolone
67
What is an antagonist of glycine?
strychnine
68
Which GABA transporters have a high affinity for GABA?
GAT-1, GAT-2, GAT-3
69
Which GABA transporters have a low affinity for GABA?
BGT-1
70
Which things block GABA transporters?
taurine, hypotaurine, L-DABA, B-alanine, tiagabine, guvacine
71
What does glycine do on NMDA channels?
it is a coagnost for it
72
Where are glycine channels at?
mostly in the spine
73
What is the transporter for glycine in neurons and astrocytes?
GLYT1
74
What is the transporter for glycine in neurons?
GLYT2
75
What blocks GLYT1?
sarcosine
76
What is a GABA B receptor agonist?
baclofen (potent!)
77
What are GABA B antagonists?
saclofen, phaclofen
78
What is a signaling mechanism GABA B receports use?
they dimerize
79
What are GABA B receports good for?
slower but longer lasting inhbibtion
80
Where are GABA B receptors in the cell?
pre and postsynaptic- they are Gi/o coupled
81
What kind of stimuli do extrasynaptic GABA B receports need?
longer duration and higher frequency
82
What is the synaptic function of a GABA B heteroreceptor?
it inhibits GABA on glutaminergic neurons
83
What is the synaptic function of a GABA B autoreceptor?
they inhibit on GABA neurons
84
GABA B receports inhibit pre-synaptic ____ channels and ____ _____ resulting in ______ transmitter release.
Ca2+, adenylyl cyclase, decreased
85
What is PSD?
post-synaptic density; a collection of proteins that recruit and anchor receports and signaling molecules
86
What is a common example of a molecule that contributes to formation of correct synapses?
neurexin/neurolignan
87
how do pre and post synaptic cells line up so that they communicate effectively?
they have the same receptor and NT
88
Extracellular pairing is an example of interaction that helps direct _____ ______.
Synaptic interactions
89
What is the job of beta-neurexin?
it aligns vesicles
90
What is the job of neurlignan?
it anchors
91
What are peptides?
polymers of amino acids linked together by amine bonds
92
What are neuropeptides?
specific peptides that act as neurotransmitters in the nervous system
93
What signals an N terminus?
an NH2
94
What is an N terminus?
the start of a protein or polypeptide terminated by an amino acid with a free amine group (-NH2)
95
What signals a C terminus?
-COOH
96
What is an C terminus?
he end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH)
97
How many main amino acids are there?
20
98
How many essential amino acids are there?
8
99
What is an amino acid?
a simple organic compound containing both a carboxyl (—COOH) and an amino (—NH2) group and it has an R side group
100
What is a neuropeptide?
small protein-like molecules (peptides) used by neurons to communicate with each other
101
What is the secondary structure of an amino acid?
a helix or beta pleated sheets
102
Neuropeptides produce neuronal responses with _____ onset and ____ duration.
slow, long
103
Neuropeptides serve what function in the cell?
modulators
104
Are ion channels directly opened by neuropeptides in mammals?
no
105
Neuropeptide recovery does not depend on ______ ________.
reuptake transporters
106
What is required for recovery for neuropeptides?
1- RNA transcription
2- protein translation
3- axonal transport
107
What neuropeptide has the opposing functions to opioids?
CCK, cholecystokinin
108
What does CCK do in the periphery?
stimulates digestion of fat and protein
109
What does CCk do in neural areas?
it induces anxiety and nausea
110
What does angiotensin do in the periphery?
it causes vasoconstriction
111
What does angiotensin do in neural areas?
thirst
112
What does oxytocin do in the periphery?
lactation, uterine contractions during labor
113
What does oxytocin do in neural areas?
anti-stress, maternal behavior, pain reduction
114
What are the four major functions of neuropeptides?
1- modulation of sensory information
2- modulation of emotion
3- learning and memory
4- feeding and energy balance
115
What does Substance P do?
enhances pain perception
116
What does calcitonin gene-related peptide do? (CGRP)
plays a role in migraines
117
What are enkephalins associated with?
reduced pain perception
118
What does CRF (corticotrophin releasing factor) play a role in?
fear and anxiety
119
What does vasopressin do?
plays a role in memory formation
120
What role do opioids play in memory?
they are thought to play a role in memory loss
121
What has NPY been linked to?
food intake and obesity
122
Where is norepinephrine produced?
pons and medulla
123
What structure contains over 50% of the NE neurons in the brain?
locus ceruleus (LC) in the pons
124
What does NE signaling contribute to?
sleep-wake cycle (arousal), attention, anxiety
125
What are NE modulating drugs used in the treatment of?
ADHD
126
NE acting on beta receptors in the amygdala ______ memory for negative emotions.
increases
127
What is the rate-limiting enzyme for NE creation?
tyrosine hydroxylase (TH)
128
TH is thought to be _____ under normal conditions.
saturated
129
What is TH inhibited by?
catecholamines (feedback inhibition)
130
What is required as a cofactor for HT?
BH4 (tetrahydrobiopterin)
131
What does AADC rquire as a cofactor?
pyroxidal-5-phosphate (derivative of B6)
132
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 _______.
L-Dopa
Dopamine
Noradrenaline
Adrenaline
133
List the order of biosynthesis of adrenaline (only the created molecules). 5 steps
```
1- tyrosine
2- L Dopa
3- Dopamine
4- Noradrenaline (norepi)
5- Adrenaline (epi)
```
134
What are the four molecules that act on molecules to aid in biosynthesis of adrenaline.
1- TH (tyrosine hydroxylase)
2- L-AADC (L Aromatic amino acid)
3- DBH (dopamine beta hydroxylase)
4- phenylethanoamine N-methyltransferase
135
What are the steps of synthesis of serotonin? 3 molecules
1- tryptophan
2- 5 HTP
3- 5 HT (serotonin)
136
What does serotonin lead to synthesis of?
melatonin
137
What molecule acts on tryptophan to lead to synthesis of 5 htp?
tryptophan hydroxylase
138
What molecule acts of 5 HTP to lead to synthesis of 5 HT (aka serotonin)?
L-AADC
139
What two things degrade catecholamines?
MAO or COMT
140
MAO A is mostly in _______ neurons and metabolizes 5HT, ____, epi, ____ and tyramine.
norandrenergic neurons, NE, DA
141
MAO B is mostly in _______ and ________ neurons and metabolizes DA.
serotonergic and histaminergic
142
What do MAO inhibitors inhibit the breakdown of?
catecholamines
143
What are some examples of MAOIs?
isocarboxazid, phenelzine, tranylcypromine, selegiline
144
What does VMAT transport?
monoamines (multiple)
145
Is VMAT selective?
no
146
What are the two isoforms of VMAT?
VMAT1 and VMAT2
147
What is VMAT inhibited by?
reserpine and terabenazine
148
How does guanethidine interact with NET?
it is taken up by it then concentrated in vesicles; it will eventually deplete the vesicles of NE
149
What does dopamine degrade into via MAO?
homovanillic acid
150
What does norepinephrine degrade into via MAO?
vanillylmandelic acid or MHPG
151
How are catecholamines regulated?
1- diffusion away from synapses
2- metabolic breakdown
3- reuptake into nerve terminals
152
how many transmembrane domains does NET have?
12
153
How does cocaine impact catecholamines?
it inhibits reuptake of NE, epi, and DA by blocking NET/DAT
154
How does Ritalin act on the brain?
it blocks NET/DAT but probably does not increase NET/DA release
155
How does amphetamine act on NE/DA?
it inhibits reuptake via competition and depletes NE/DA from vesicles via disruption to the proton gradient
156
How does amphetamine stimulate the efflux of NE/DA?
it phosphorylates NET/DAT
