Chemical Messengers and Excitotoxicity Flashcards
1
Q
What kind of receptors are used for EAA? (general)
A
ionotropic and metabotropic receptors
2
Q
What are the three types of ionotropic receptors?
A
NMDA, AMPA, and Kainate receptors
3
Q
What is influxed when the NMDA channel is activated?
A
calcium
4
Q
What modulatory sites are found on the NMDA receptor?
A
binding site for the EAA, binding site for glycine, magnesium binding site, and PCP binding site (also ketamine)
5
Q
what must the NMDA receptor have bound to it in order to open?
A
the EAA and a glycine molecule
6
Q
What is blocking the NMDA channel from allowing the influx of Ca2+?
A
Mg2+ molecule
7
Q
when will the Mg2+ molecule move into the ECF?
A
when the neuron become depolarized
8
Q
What happens when the EAA binds to the AMPA receptor?
A
it will open and there will be an influx of Na+ ions
9
Q
What modulatory site is found on the AMPA receptors?
A
the EAA binding site as well as a benzodiazepine modulatory site
10
Q
what is the effect of a benzodiazepine binding to an AMPA receptor?
A
it reduces the amount of sodium that enters into the cell
11
Q
What is unique to the Kainate receptor?
A
a small amount of Ca2+ will follow the entry of Na+ into the cell once the receptor is activated
12
Q
What specifically depolarizes the NMDA receptor?
A
when the non-NMDA receptor is activated, there is an influx of Na+ into the cell, which produces a typical epsp, which will depolarize the NMDA channel and cause the Mg2+ to leave the receptor
13
Q
What are the main functions of the non-NMDA receptors?
A
primary sensory afferents and upper motor neurons
14
Q
what are the main functions of the NMDA receptors?
A
they are critical in short and long term memory formation and synaptic plasticity
15
Q
how many groups are the metabotropic receptors divided into?
A
3
16
Q
The group I metabotropic receptors are coupled to what G protein?
A
Gq
17
Q
Groups 2 and 3 metabotropic receptors are coupled to what G protein?
A
Gi
18
Q
what happens when a Gq protein is activated?
A
it causes an increase in IP3 and DAG which ultimately causes Ca2+ to be released intracellularly
19
Q
what happens when a Gi protein is activated?
A
there is going to be a decrease in cAMP
20
Q
what is the main function of pre-synaptic metabotropic receptors for EAAs?
A
they control NT release
21
Q
what is the main function of post-synaptic metabotropic receptors for EAAs?
A
learning, memory, and motor systems
22
Q
How do you limit the action of the EAA?
A
glial cells around the pre- and post-synaptic neurons have transporter proteins on them that take up the EAA
23
Q
What does the transporter protein on the glial cell require?
A
the Na/K ATPase–> it is Na dependent
24
Q
inside the glial cell, what happens to the EAA?
A
it is converted into glutamine
25
what happens to the glutamine once it is converted in the glial cell?
it is moved out of the glial cell and into the pre-synaptic cell
26
what happens to the glutamine once inside the pre-synaptic neuron?
it is going to be converted back into an EAA and then repackaged into the vesicle
27
What does calcium bind to once it flows inside the neuron?
calcineurin
28
what happens when calcium binds to calcineurin?
it is going to activate NOS
29
What does the NOS do?
it takes the AA arginine and cleaves off a nitric oxide (NO), giving us NO and citruline
30
What are the neural functions of NO?
effects on memory, cardiovascular and respiratory control
31
what are the non-neural functions of NO?
immunological effects and EDRF (endothelial derived relaxing factor)--> causes relaaxation of smooth muscle--> vasodilation
32
What are the harms of NO?
very unstable, leads to the production of free radicals, in high concentrations it is toxic to neurons
33
What are the 5 monoamines?
epinephrine, norepinephrine, dopamine, serotonin, and histamine
34
Where do you find the norepinephrine neurons?
locus ceruleus and other pontine/ medullary areas
35
where is the locus ceruleus found?
down in the brainstem
36
what is the role of norepinephrine?
wakefulness/ alertness
37
where do you find epinephrine neurons?
medulla
38
what is the role of epinephrine?
modulatory role
39
From which amino acid is dopamine, norepinephrine, and epinephrine derived?
tyrosine
40
what enzyme converts tyrosine into L-DOPA?
tyrosine hydroxylase
41
what happens once tyrosine is converted into L-DOPA?
it is then moved into vesicles and the norepinephrine is created if there is an enzyme for that inside the vesicle
42
what is the enzyme that converts norepinephrine into epinephrine?
PNMT
43
where does the conversion of norepinephrine into epinephrine occur?
outside the vesicle and then the epinephrine is moved back inside the vesicle
44
How is the norepinephrine/ epinephrine moved into the vesicles?
by the VMATs 1 and 2
45
what drug inhibits the VMATs?
reserpine
46
how is the action of norepinephrine, epinephrine, and dopamine limited?
reuptake and enzymatic degradation by MAO and COMT
47
what are the receptors for norepinephrine and epinephrine?
alpha and beta adrenergic
48
where do you find dopamanergic neurons?
in the basal ganglia, in the hypothalamus and limbic system, and in the cortex
49
what is the function of the dopamanergic neurons found in the basal ganglia?
motor control
50
what is the function of the dopamanergic neurons found in the hypothalamus and the limbic system?
they are involved in endocrine and emotional control
51
what are the receptors for dopamine?
there are 5 metabotropic receptors
52
what are the D1 and D5 receptors bound to?
a Gs protein
53
what happens when a Gs protein is activated?
there is an increase in cAMP
54
what are the D2 receptors bound to?
a Gi protein
55
what happens when a Gi protein is activated?
there is a decrease in cAMP, which causes a potassium efflux, which causes hyperpolarization of the cell
56
what are the D3 and D4 receptors bound to?
a Gi protein
57
where are the serotengeric neurons found?
in the cerebellum, in the raphe nuclei, and in the hypothalamus and limbic system
58
what is the function of the serotenergic neurons found in the hypothalamus and limbic system?
mood
59
what is the function of the serotenergic neurons found in the cerebellum?
modification of motor activity
60
what is the function of the serotenergic neurons found in the Raphe nuclei?
modification of motor and sensory activity
61
what amino acid is serotonin derived from?
tryptophan
62
what converts tryptophan into serotonin?
tryptophan hydroxylase
63
how do you limit the actions of serotonin?
reuptake and catabolism by MAO and COMT
64
what are the receptors for serotonin?
there are 7 with multiple subtypes, most of them are metabotropic but there is one ionotropic receptor
65
what happens when the 5HT3 receptors are activated?
vomiting
66
what happens when the 5HT6 receptors are activated?
there is an anti-depressant effect
67
where do you find histamine neurons?
tuberomammillary nucleus of the hypothalamus
68
what is the role of histamine in the tuberomammillary nucleus of the hypothalamus?
wakefulness
69
what amino acid is histamine derived from?
histidine
70
what enzyme is used to convert histidine into histamine?
histidine decarboxylase
71
how do you limit the actions of histamine?
reuptake and catabolism of diamine oxidase (DAO) and COMT
72
what are the receptors for histamine?
H1, H2, and H3
73
what type of receptors are the histamine receptors?
metabotropic receptors
74
which receptor for histamine is involved in wakefulness?
H1
75
what are the two major inhibitory amino acids?
GABA and glycine
76
where is the most amount of GABA found?
widely distributed throughout higher levels of the CNS
77
GABA is critical in what functions?
consciousness, motor control, and vision (retina)
78
what is GABA synthesized from?
glutamate
79
what is the enzyme that converts glutamate into GABA?
glutamate decarboxylase (GAD)
80
how is GABA transported into vesicles?
by vesicular GABA transporter protein
81
how is GABA removed from the synapse?
via GAT (two different forms)
82
where is GAT 1 found?
on the presynaptic terminal
83
where is GAT 2 found?
on glial cells surrounding the synapse
84
what happens if GAT1 takes up the GABA?
the GABA is repackaged into vesicles
85
what happens if GAT2 takes up the GABA?
the GABA is converted to glutamate then to glutamine and then released into the ECF where it will be taken up by the presynaptic terminal and recycled into GABA
86
What are the different types of GABA receptors?
GABA a and GABA b
87
what type of receptor is GABA a?
ionotropic (Cl-)
88
what happens when GABA a receptors are activated?
Cl- flows into the cell and the GABAa receptors produce ipsp in adult neurons
89
what are the other binding sites on the GABAa receptors?
benzodiazepine sites, ethanol sites, and certain steroids
90
what are the other binding sites on the GABAa receptors known to be?
potentiate, which means that they all increase the amount of Cl- that flows into the channel--> bigger ipsp--> cell is more inhibited
91
what was discovered to be special about the GABAa receptors?
it appears that there are large numbers of extra-synaptic GABAa receptors
92
what is the significance of extra-synaptic GABAa receptors?
they are believed to be the site of action for a number of general anesthetics, including propofol
93
what type of receptor is a GABAb receptor?
metabotropic
94
what is the GABAb receptor bound to?
a Gi/G0 protein
95
what happens when the Gi/G0 is activated?
a K+ channel is activated and a Ca2+ channel is inhibited
96
what is the role of GABAb receptors located pre-synaptically?
regulate NT release
97
what is the role of GABAb receptors located post-synaptically?
inhibition of post-synaptic cell
98
what is the function of glycine?
mediates many spinal inhibitions
99
what is glycine produced by?
unmodified amino acid
100
how do you remove glycine from the synapse?
GAT proteins and recycling
101
what type of receptor is the glycine receptor?
ionotropic (chloride)
102
what does an influx of chlorine lead to?
IPSP
103
what else can bind to a glycine receptor?
ethanol and general anesthetics (potentiate it) and strychnine (blocks it)
104
What are the purines?
ATP, ADP, and adenosine
105
what synthesizes ATP in the pre-synaptic terminal?
mitochondria
106
where are the regions where more purines are found?
cortex, cerebellum, basal ganglia, hippocampus
107
What are the receptors for adenosine?
P1
108
what is the function of post-synaptic adenosine receptors?
sleep induction and general inhibition of neural function
109
what is the function of pre-synaptic adenosine receptors?
inhibition of NT release
110
What type of receptor is the P2X receptor?
ionotropic
111
what is the ligand for the P2X receptor?
ATP
112
what type of receptor is the P2Y receptor?
metabotropic
113
what is the ligand for the P2Y receptor?
ATP, ADP, UTP, UDP
114
What is the P2Y receptor bound to?
a Gi/Gq protein
115
What is an example of a benzodiazepine?
valium (muscle relaxant)
116
What happens when histamine binds to the H1 receptor?
PLC activation
117
what happens when histamine binds to the H2 receptor?
increased CAMP (associated with gastric acid release)
118
what happens when histamine binds to the H3 receptor?
it is presynaptic, so it will cause a decrease in histamine release
119
the opioids are a family of peptides that include?
endorphins, enkephalins, dynorphins, and nociceptin
120
Where do you find the opioids?
basal ganglia, hypothalamus, and pontine and medullary sites
121
What are the general functions of the opioids?
modification of nociceptive inputs, mood/affect
122
what is the precursor of B-endorphins?
proopiomelanocortinin (POMC)
123
what is POMC the precursor to?
ACTH
124
what is the 4 AA chain precursor to the encephalins?
tyrosine-glysine-glysine-phenelalanine
125
what is the precursor for dynorphine?
pro-dynorphine (3 molecules of leu-enkephalin
126
what is the precursor for nociceptin?
orphanin FQ
127
how do you remove the opioids from the trough/cleft?
reuptake and enzymatic destruction
128
what are the two forms of enzymatic destruction for the opioids?
enkephalinase and aminopeptidiase
129
what type of receptors are the 3 receptors for the opioids?
metabotropic
130
what are the three receptors for the opioids?
mu-receptor, kappa-receptor, delta-receptor
131
what does activation of the mu-receptor cause?
analgesia, respiratory depression, euphoria, constipation, and sedation
132
what does activation of the kappa-receptor cause?
analgesia and dysphoria
133
what does activation of the delta-receptor cause?
analgesia only
134
what are all the metabotropic receptors for the opioids bound to?
Gi/G0 proteins
135
what happens to the Gi/G0 protein when the mu-receptor is activated?
it leads to an increase in potassium efflux and hyperpolarization
136
what happens to the Gi/G0 protein when the delta and kappa receptors are activated?
there is a decrease in calcium influx
137
what are the 2 identified endogenous endocannabinoids?
anadamide and 2-AG
138
where are the endocannabinoids found?
in the basal ganglia, spinal cord, and cortex
139
what is the function of the endocannabinoids in the basal ganglia?
mood and motor performance
140
what is the function of the endocannabinoids in the spinal cord?
modulation of nociception
141
what is the function of the endocannabinoids in the cortex?
neuroprotection
142
what are the endocannabinoids derived from?
membrane lipids (specifically arachidonic acid)
143
where does the endocannabinoid synthesis take place?
in the presynaptic terminal
144
what specific membrane lipid is the anandamide derived from?
NAPE
145
what specific membrane lipid is the 2AG derived from?
PIP2
146
What are the two receptors for the cannabinoids?
CB1 and CB2
147
what is activation of the CB1 associated with?
the psychoactive responses to the cannabinoids
148
where are the CB1 receptors located?
central nervous system neurons
149
where is the synaptic location of the cannabinoid receptors?
largely presynaptic
150
what is the effect of the CB1 receptors on EAA and GABA?
they reduce EAA and GABA release via a G1 coupled protein
151
where are CB2 receptors found in the brain?
on microglia
152
what would you suspect if there were CB2 receptors found on neurons (dendrites and within the soma)?
nerve injury
153
what does the CB2 have a higher affinity for?
2AG better than AEA
154
How can you degrade endocannabinoids?
hydrolysis or oxidation
155
how is anandamide degraded via hydrolysis?
Fatty acid amide hydrolase (FAAH)
156
how is 2AG degraded via hydrolysis?
mono-acyl glycerol lipase (MAGL)
157
how are both AEA and 2AG degraded via oxidation?
cyclooxygenase and lipooxygenase pathway
