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Neuroendocrine Exam 2 > Chemical Messengers and Excitotoxicity > Flashcards

Chemical Messengers and Excitotoxicity Flashcards

1
Q

What kind of receptors are used for EAA? (general)

A

ionotropic and metabotropic receptors

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2
Q

What are the three types of ionotropic receptors?

A

NMDA, AMPA, and Kainate receptors

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3
Q

What is influxed when the NMDA channel is activated?

A

calcium

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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)

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5
Q

what must the NMDA receptor have bound to it in order to open?

A

the EAA and a glycine molecule

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6
Q

What is blocking the NMDA channel from allowing the influx of Ca2+?

A

Mg2+ molecule

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7
Q

when will the Mg2+ molecule move into the ECF?

A

when the neuron become depolarized

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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

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9
Q

What modulatory site is found on the AMPA receptors?

A

the EAA binding site as well as a benzodiazepine modulatory site

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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

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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

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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

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13
Q

What are the main functions of the non-NMDA receptors?

A

primary sensory afferents and upper motor neurons

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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

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15
Q

how many groups are the metabotropic receptors divided into?

A

3

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16
Q

The group I metabotropic receptors are coupled to what G protein?

A

Gq

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17
Q

Groups 2 and 3 metabotropic receptors are coupled to what G protein?

A

Gi

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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

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19
Q

what happens when a Gi protein is activated?

A

there is going to be a decrease in cAMP

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20
Q

what is the main function of pre-synaptic metabotropic receptors for EAAs?

A

they control NT release

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21
Q

what is the main function of post-synaptic metabotropic receptors for EAAs?

A

learning, memory, and motor systems

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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

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23
Q

What does the transporter protein on the glial cell require?

A

the Na/K ATPase–> it is Na dependent

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24
Q

inside the glial cell, what happens to the EAA?

A

it is converted into glutamine

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25
Q

what happens to the glutamine once it is converted in the glial cell?

A

it is moved out of the glial cell and into the pre-synaptic cell

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26
Q

what happens to the glutamine once inside the pre-synaptic neuron?

A

it is going to be converted back into an EAA and then repackaged into the vesicle

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27
Q

What does calcium bind to once it flows inside the neuron?

A

calcineurin

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28
Q

what happens when calcium binds to calcineurin?

A

it is going to activate NOS

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29
Q

What does the NOS do?

A

it takes the AA arginine and cleaves off a nitric oxide (NO), giving us NO and citruline

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30
Q

What are the neural functions of NO?

A

effects on memory, cardiovascular and respiratory control

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31
Q

what are the non-neural functions of NO?

A

immunological effects and EDRF (endothelial derived relaxing factor)–> causes relaaxation of smooth muscle–> vasodilation

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32
Q

What are the harms of NO?

A

very unstable, leads to the production of free radicals, in high concentrations it is toxic to neurons

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33
Q

What are the 5 monoamines?

A

epinephrine, norepinephrine, dopamine, serotonin, and histamine

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34
Q

Where do you find the norepinephrine neurons?

A

locus ceruleus and other pontine/ medullary areas

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35
Q

where is the locus ceruleus found?

A

down in the brainstem

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36
Q

what is the role of norepinephrine?

A

wakefulness/ alertness

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37
Q

where do you find epinephrine neurons?

A

medulla

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38
Q

what is the role of epinephrine?

A

modulatory role

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39
Q

From which amino acid is dopamine, norepinephrine, and epinephrine derived?

A

tyrosine

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40
Q

what enzyme converts tyrosine into L-DOPA?

A

tyrosine hydroxylase

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41
Q

what happens once tyrosine is converted into L-DOPA?

A

it is then moved into vesicles and the norepinephrine is created if there is an enzyme for that inside the vesicle

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42
Q

what is the enzyme that converts norepinephrine into epinephrine?

A

PNMT

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43
Q

where does the conversion of norepinephrine into epinephrine occur?

A

outside the vesicle and then the epinephrine is moved back inside the vesicle

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44
Q

How is the norepinephrine/ epinephrine moved into the vesicles?

A

by the VMATs 1 and 2

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45
Q

what drug inhibits the VMATs?

A

reserpine

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46
Q

how is the action of norepinephrine, epinephrine, and dopamine limited?

A

reuptake and enzymatic degradation by MAO and COMT

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47
Q

what are the receptors for norepinephrine and epinephrine?

A

alpha and beta adrenergic

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48
Q

where do you find dopamanergic neurons?

A

in the basal ganglia, in the hypothalamus and limbic system, and in the cortex

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49
Q

what is the function of the dopamanergic neurons found in the basal ganglia?

A

motor control

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50
Q

what is the function of the dopamanergic neurons found in the hypothalamus and the limbic system?

A

they are involved in endocrine and emotional control

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51
Q

what are the receptors for dopamine?

A

there are 5 metabotropic receptors

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52
Q

what are the D1 and D5 receptors bound to?

A

a Gs protein

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53
Q

what happens when a Gs protein is activated?

A

there is an increase in cAMP

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54
Q

what are the D2 receptors bound to?

A

a Gi protein

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55
Q

what happens when a Gi protein is activated?

A

there is a decrease in cAMP, which causes a potassium efflux, which causes hyperpolarization of the cell

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56
Q

what are the D3 and D4 receptors bound to?

A

a Gi protein

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57
Q

where are the serotengeric neurons found?

A

in the cerebellum, in the raphe nuclei, and in the hypothalamus and limbic system

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58
Q

what is the function of the serotenergic neurons found in the hypothalamus and limbic system?

A

mood

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59
Q

what is the function of the serotenergic neurons found in the cerebellum?

A

modification of motor activity

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60
Q

what is the function of the serotenergic neurons found in the Raphe nuclei?

A

modification of motor and sensory activity

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61
Q

what amino acid is serotonin derived from?

A

tryptophan

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62
Q

what converts tryptophan into serotonin?

A

tryptophan hydroxylase

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63
Q

how do you limit the actions of serotonin?

A

reuptake and catabolism by MAO and COMT

64
Q

what are the receptors for serotonin?

A

there are 7 with multiple subtypes, most of them are metabotropic but there is one ionotropic receptor

65
Q

what happens when the 5HT3 receptors are activated?

A

vomiting

66
Q

what happens when the 5HT6 receptors are activated?

A

there is an anti-depressant effect

67
Q

where do you find histamine neurons?

A

tuberomammillary nucleus of the hypothalamus

68
Q

what is the role of histamine in the tuberomammillary nucleus of the hypothalamus?

A

wakefulness

69
Q

what amino acid is histamine derived from?

A

histidine

70
Q

what enzyme is used to convert histidine into histamine?

A

histidine decarboxylase

71
Q

how do you limit the actions of histamine?

A

reuptake and catabolism of diamine oxidase (DAO) and COMT

72
Q

what are the receptors for histamine?

A

H1, H2, and H3

73
Q

what type of receptors are the histamine receptors?

A

metabotropic receptors

74
Q

which receptor for histamine is involved in wakefulness?

A

H1

75
Q

what are the two major inhibitory amino acids?

A

GABA and glycine

76
Q

where is the most amount of GABA found?

A

widely distributed throughout higher levels of the CNS

77
Q

GABA is critical in what functions?

A

consciousness, motor control, and vision (retina)

78
Q

what is GABA synthesized from?

A

glutamate

79
Q

what is the enzyme that converts glutamate into GABA?

A

glutamate decarboxylase (GAD)

80
Q

how is GABA transported into vesicles?

A

by vesicular GABA transporter protein

81
Q

how is GABA removed from the synapse?

A

via GAT (two different forms)

82
Q

where is GAT 1 found?

A

on the presynaptic terminal

83
Q

where is GAT 2 found?

A

on glial cells surrounding the synapse

84
Q

what happens if GAT1 takes up the GABA?

A

the GABA is repackaged into vesicles

85
Q

what happens if GAT2 takes up the GABA?

A

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
Q

What are the different types of GABA receptors?

A

GABA a and GABA b

87
Q

what type of receptor is GABA a?

A

ionotropic (Cl-)

88
Q

what happens when GABA a receptors are activated?

A

Cl- flows into the cell and the GABAa receptors produce ipsp in adult neurons

89
Q

what are the other binding sites on the GABAa receptors?

A

benzodiazepine sites, ethanol sites, and certain steroids

90
Q

what are the other binding sites on the GABAa receptors known to be?

A

potentiate, which means that they all increase the amount of Cl- that flows into the channel–> bigger ipsp–> cell is more inhibited

91
Q

what was discovered to be special about the GABAa receptors?

A

it appears that there are large numbers of extra-synaptic GABAa receptors

92
Q

what is the significance of extra-synaptic GABAa receptors?

A

they are believed to be the site of action for a number of general anesthetics, including propofol

93
Q

what type of receptor is a GABAb receptor?

A

metabotropic

94
Q

what is the GABAb receptor bound to?

A

a Gi/G0 protein

95
Q

what happens when the Gi/G0 is activated?

A

a K+ channel is activated and a Ca2+ channel is inhibited

96
Q

what is the role of GABAb receptors located pre-synaptically?

A

regulate NT release

97
Q

what is the role of GABAb receptors located post-synaptically?

A

inhibition of post-synaptic cell

98
Q

what is the function of glycine?

A

mediates many spinal inhibitions

99
Q

what is glycine produced by?

A

unmodified amino acid

100
Q

how do you remove glycine from the synapse?

A

GAT proteins and recycling

101
Q

what type of receptor is the glycine receptor?

A

ionotropic (chloride)

102
Q

what does an influx of chlorine lead to?

A

IPSP

103
Q

what else can bind to a glycine receptor?

A

ethanol and general anesthetics (potentiate it) and strychnine (blocks it)

104
Q

What are the purines?

A

ATP, ADP, and adenosine

105
Q

what synthesizes ATP in the pre-synaptic terminal?

A

mitochondria

106
Q

where are the regions where more purines are found?

A

cortex, cerebellum, basal ganglia, hippocampus

107
Q

What are the receptors for adenosine?

A

P1

108
Q

what is the function of post-synaptic adenosine receptors?

A

sleep induction and general inhibition of neural function

109
Q

what is the function of pre-synaptic adenosine receptors?

A

inhibition of NT release

110
Q

What type of receptor is the P2X receptor?

A

ionotropic

111
Q

what is the ligand for the P2X receptor?

A

ATP

112
Q

what type of receptor is the P2Y receptor?

A

metabotropic

113
Q

what is the ligand for the P2Y receptor?

A

ATP, ADP, UTP, UDP

114
Q

What is the P2Y receptor bound to?

A

a Gi/Gq protein

115
Q

What is an example of a benzodiazepine?

A

valium (muscle relaxant)

116
Q

What happens when histamine binds to the H1 receptor?

A

PLC activation

117
Q

what happens when histamine binds to the H2 receptor?

A

increased CAMP (associated with gastric acid release)

118
Q

what happens when histamine binds to the H3 receptor?

A

it is presynaptic, so it will cause a decrease in histamine release

119
Q

the opioids are a family of peptides that include?

A

endorphins, enkephalins, dynorphins, and nociceptin

120
Q

Where do you find the opioids?

A

basal ganglia, hypothalamus, and pontine and medullary sites

121
Q

What are the general functions of the opioids?

A

modification of nociceptive inputs, mood/affect

122
Q

what is the precursor of B-endorphins?

A

proopiomelanocortinin (POMC)

123
Q

what is POMC the precursor to?

A

ACTH

124
Q

what is the 4 AA chain precursor to the encephalins?

A

tyrosine-glysine-glysine-phenelalanine

125
Q

what is the precursor for dynorphine?

A

pro-dynorphine (3 molecules of leu-enkephalin

126
Q

what is the precursor for nociceptin?

A

orphanin FQ

127
Q

how do you remove the opioids from the trough/cleft?

A

reuptake and enzymatic destruction

128
Q

what are the two forms of enzymatic destruction for the opioids?

A

enkephalinase and aminopeptidiase

129
Q

what type of receptors are the 3 receptors for the opioids?

A

metabotropic

130
Q

what are the three receptors for the opioids?

A

mu-receptor, kappa-receptor, delta-receptor

131
Q

what does activation of the mu-receptor cause?

A

analgesia, respiratory depression, euphoria, constipation, and sedation

132
Q

what does activation of the kappa-receptor cause?

A

analgesia and dysphoria

133
Q

what does activation of the delta-receptor cause?

A

analgesia only

134
Q

what are all the metabotropic receptors for the opioids bound to?

A

Gi/G0 proteins

135
Q

what happens to the Gi/G0 protein when the mu-receptor is activated?

A

it leads to an increase in potassium efflux and hyperpolarization

136
Q

what happens to the Gi/G0 protein when the delta and kappa receptors are activated?

A

there is a decrease in calcium influx

137
Q

what are the 2 identified endogenous endocannabinoids?

A

anadamide and 2-AG

138
Q

where are the endocannabinoids found?

A

in the basal ganglia, spinal cord, and cortex

139
Q

what is the function of the endocannabinoids in the basal ganglia?

A

mood and motor performance

140
Q

what is the function of the endocannabinoids in the spinal cord?

A

modulation of nociception

141
Q

what is the function of the endocannabinoids in the cortex?

A

neuroprotection

142
Q

what are the endocannabinoids derived from?

A

membrane lipids (specifically arachidonic acid)

143
Q

where does the endocannabinoid synthesis take place?

A

in the presynaptic terminal

144
Q

what specific membrane lipid is the anandamide derived from?

A

NAPE

145
Q

what specific membrane lipid is the 2AG derived from?

A

PIP2

146
Q

What are the two receptors for the cannabinoids?

A

CB1 and CB2

147
Q

what is activation of the CB1 associated with?

A

the psychoactive responses to the cannabinoids

148
Q

where are the CB1 receptors located?

A

central nervous system neurons

149
Q

where is the synaptic location of the cannabinoid receptors?

A

largely presynaptic

150
Q

what is the effect of the CB1 receptors on EAA and GABA?

A

they reduce EAA and GABA release via a G1 coupled protein

151
Q

where are CB2 receptors found in the brain?

A

on microglia

152
Q

what would you suspect if there were CB2 receptors found on neurons (dendrites and within the soma)?

A

nerve injury

153
Q

what does the CB2 have a higher affinity for?

A

2AG better than AEA

154
Q

How can you degrade endocannabinoids?

A

hydrolysis or oxidation

155
Q

how is anandamide degraded via hydrolysis?

A

Fatty acid amide hydrolase (FAAH)

156
Q

how is 2AG degraded via hydrolysis?

A

mono-acyl glycerol lipase (MAGL)

157
Q

how are both AEA and 2AG degraded via oxidation?

A

cyclooxygenase and lipooxygenase pathway

Neuroendocrine Exam 2 (17 decks)

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