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Neurotransmitter Systems Flashcards

1
Q

What are the 5 monoamines?

A
  • Norepinephrine
  • Epinephrine
  • Dopamine
  • Serotonin
  • Histamine
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2
Q

Norepinephrine: Location

A
  • Locus Ceruleus
  • Medulla
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3
Q

Norepinephrine: Functions

A

Wakefulness/Arousal

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4
Q

Norepinephrine: Ionotropic Receptors

A

NA

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5
Q

Norepinephrine: Metabotropic Receptors

A
  • Alpha-Adrenergic
  • Beta-Adrenergic
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6
Q

What is Norepinephrine derieved from?

A

Tyrosine

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7
Q

Epinephrine: Location

A

Medulla

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8
Q

Epinephrine: Function

A

Modulatory

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9
Q

Epinephrine: Ionotropic Receptors

A

NA

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10
Q

Epinephrine: Metabotropic Receptors

A
  • Alpha-Adrenergic
  • Beta-Adrenergic
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11
Q

What is Epinephrine derived from?

A

Tyrosine

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12
Q

Steps of NE/Epi Synthesis

A

(1) Tyrosine Hydroxylase converts tyrosine to DOPA (RLS)
(2) DOPA moved into vesicles
(3) Dopamine –> NE
(4) NE leaves vesicles
(5) If the neuron has PNMT, then it converts NE to Epi after NE leaves the vesicles
(6) Epi moved back into vesicles

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13
Q

Proteins that move Epinephrine into vesicles:

A

Vesicular MonoAmine Transport Proteins – VMAT1 and VMAT2

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14
Q

Reserpine

A
  • Drug
  • Inhibits movement of Epi back into vesicle
  • Leads to synaptic failure
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15
Q

2 Major Methods that limit the action of Epi and NE:

A
  • Reuptake
  • Enzymatic degradation (Monoamine Oxidase, Catechol-O-methyl Transferase)
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16
Q

Monoamine Oxidase

A
  • Located on outer surface of mitochondria
  • Metabolites from breakdown of NTs are released into ECF
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17
Q

Catechol-O-Methyl Transferase

A

Located on Glial cells and post-synaptic membrane – cleans up the NE/Epi that doesn’t get taken back into the presynaptic cell initially

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18
Q

Serpentine Receptors

A
  • Metabotropic receptors
  • Work via 2nd messengers
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19
Q

Dopamine: Location

A
  • Substantia Nigra
  • VTA (Ventral Tegmental Area; input to basal ganglia)
  • Cortex
  • Hypothalamus
  • Limbic System
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20
Q

Role of Dopamine in Basal Ganglia:

A

Motor control

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21
Q

Role of Dopamine in Hypothalamus and Limbic System:

A

Endocrine and emotional control

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22
Q

Dopamine: Functions

A
  • Mood
  • Affect
  • Hormonal
  • General arousal
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23
Q

Dopamine: Ionotropic Receptors

A

NA

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24
Q

Dopamine: Metabotropic Receptors

A
  • D1
  • D2
  • D3
  • D4
  • D5
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25
Dopamine: D1 and D5 Receptors
- Connected to Gs protein - Increase cAMP (via increased adenylate cyclase activity)
26
Dopamine: D2 Receptors
- Connected to Gi protein - Decrease in cAMP (via decreased adenylate cyclase activity) --> increased Potassium Efflux (creates hyperpolarization of the cell)
27
Dopamine: D3 and D4 Receptors
- Connected to Gi protein - Leads to decreased cAMP (via decreased adenylate cyclase activity)
28
Serotonin: Location
- Hypothalamus - Limbic System - Cerebellum - Raphe Nuclei (located in brainstem)
29
Role of Serotonin in Hypothalamus and Limbic System:
Mood
30
Role of Serotonin in Raphe Nuclei:
Modification of motor and sensory activity
31
Role of Serotonin in Cerebellum:
Modification of motor activity
32
What is Serotonin derived from?
Tryptophan (via Tryptophan Hydroxylase enzyme)
33
Serotonin: Functions
- Mood and affect - Arousal - Modification of sensory and motor inputs
34
Serotonin: Ionotropic Receptors
5HT3 (Na+ influx)
35
Serotonin: Metabotropic Receptors
- 5HT1 - 5HT2 - 5HT4 - 5HT5 - 5HT6
36
What happens if 5HT3 is activated in the Area Postrema?
Vomiting
37
What is the effect of Serotonin binding to 5HT6?
Ani-depressant effect
38
Histamine: Location
Hypothalamus --- specifically the Tuberomammillary Nucleus
39
Histamine: Functions
Arousal
40
Histamine: Ionotropic Receptors
NA
41
Histamine: Metabotropic Receptors
- H1 - H2 - H3
42
Histamine: H1 Receptor
- Binding leads to PLC activation - Involved in wakefulness - Largely peripheral
43
Histamine: H2 Receptor
- Binding leads to increase cAMP - Associated with gastric acid release - Largely peripheral
44
Histamine: H3 Receptor
- Presynaptic receptor - Binding leads to decreased histamine release -- part of feedback system; tells cell 'you have released enough histamine and can stop now'
45
Acetylcholine: Location
- Pons and Midbrain - Striatum (Caudate + Putamen) of Basal Ganglia
46
Acetylcholine Function in the Striatum
Control of voluntary motion
47
Acetylcholine Function in the Midbrain and Pons
- Baseline excitation to cortex (brain arousal mechanisms) - REM sleep
48
Acetylcholine: Function
- Wakefulness - Motor Control
49
Acetylcholine: Ionotropic Receptors
Nicotinic
50
Acetylcholine: Location of Nicotinic Receptors
- Thalamus - Cortex (diffusely)
51
Acetylcholine: Nicotinic Receptors
- 5 subunits coded for by 16 different genes - Changing the subunits changes the properties of the channel; in some central synapses it creates a nicotinic channel that allows more calcium in
52
Acetylcholine: Synthesis
- Choline and Acetate - Moved into vesicles via Vesicular ACh Transporter Protein (VAchT) - Removed from synaptic space via Acetylcholinesterase bound to post-synaptic cell membrane
53
Acetylcholine: Metabotropic Receptors
- M1 (neuronal): leads to increase in IP3/DAG (Gq) --> increased Ca++ into cell - M4: presynaptic autoreceptor, located in striatum of basal ganglia, leads to decreased cAMP (Gi) - M5: cerebrovasculature (located in large blood vessels), dopaminergic neurons of basal ganglia, leads to increase in IP3/DAG (Gq)
54
Acetylcholine: Notes
Different from the ACh found in the NMJ and ANS
55
Two major inhibitory amino acids:
(1) GABA (2) Glycine
56
What is the major inhibitory AA NT found in the CNS?
GABA
57
Location in CNS that contains the lease amount of GABA:
Spinal Cord
58
GABA: Central Location
Higher CNS - Cortex - Cerebellum - Basal Ganglia
59
GABA: Critical Functions
- Consciousness - Motor Control - Vision (retina)
60
GABA: Ionotropic Receptors
GABA(A)
61
GABA: Synthesis
- Glutamate --> GABA via Glutamate Decarboxylase (GAD) - Transported into vesicels by Vesicular GABA Transporter Protein (VGAT) - Removed from synapses via GAT (GABA Transporter)
62
GABA: GAT
- GAT1: located on presynaptic terminal, involved in reuptake - GAT2: located on glial cells surrounding the synapse, involved in reuptake and further modification
63
GABA: GAT1
- Takes GABA back up into presynaptic Terminal - Repackages GABA into vesicles as is
64
GABA: GAT2
- Astrocytes take GABA in - Convert GABA to Glutamine and released into ECF - Once in ECF it is taken up by presynaptic terminal and recycled into GABA
65
GABA: Ionotropic Receptors - GABA(A)
- When GABA binds, it opens the channel and allows Cl- to enter the cell - Activation produces IPSP (hyperpolarization) in adult neurons - Multiple modulatory sites: Benzodiazepine (sedatives), ethanol, Steroids -- allow potentiate meaning they allow more Cl- into the cell
66
There are many ___-____ GABA(A) receptors
Extra-synaptic (believe these receptors are the site of action for many general anesthetics including Propofol -- hyperpolarize the cell until you lose consciousness)
67
GABA: Metabotropic Receptors
GABA(B)
68
GABA: Metabotropic Receptors - GABA(B)
- Gi/Go protein coupled -- leads to decreased cAMP which results in activation of a K+ channel (GIRK) that allows K+ to exit the cell, hyperpolarization, reduced excitability; also closes down (inhibits) a Ca++ channel - Located pre- and post-synaptically - Presynaptic regulates NT release (via negative feedback) - Postsynaptic leads to inhibition of post-synaptic cell
69
Glycine: Location
- Spinal Cord - Lower CNS
70
Glycine: Function
General inhibition
71
Glycine: Ionotropic Receptors
GlyR
72
Glycine: Metabotropic Receptors
None
73
Glycine: Ionotropic Receptors - GlyR
- Binding opens a Cl- channel which allows Cl- to open the cell and create IPSPs - Ethanol and general anesthetics bind to this channel and potentiate (increase Cl- influx) - Strychine binds to it and blocks it -- blocking of glycine receptors leads to severe convulsions b/c glycine is critical in keeping excitability in-line
74
Purines (ATP, ADP, Adenosine): Location
Widespread (cortex, cerebellum, hippocampus, basal ganglia, hypothalamus)
75
Purines (Adenosine): Function
- Sleep - Inhibition
76
Purines (ATP): Functions
Multiple -- found in every NT vesicle in presynaptic terminal
77
Purines (ATP, ADP, Adenosine): Synthesis
- ATP by mitochondria (presyn terminal has many mitochondria) - Stored in vesicles (VNUT protein) - Released - ATP --> ADP --> Adenosine; occurs in synaptic trough
78
Purines (ATP, ADP, Adenosine): Ionotropic Receptors
P2X
79
Purines (ATP, ADP, Adenosine): Metabotropic Receptors
- P1(A) - P2Y
80
Purines (ATP, ADP, Adenosine): P2 (P2X, P2Y) Receptor Functions
- Learning and memory (co-release with EAA) - Modification of locomotor pathways
81
Purines (ATP, ADP, Adenosine): Ionotropic Receptors - P2X
- Ligand: ATP - Many subtypes - Binding of ATP leads to influx of Na+ and Ca++ into the neuron --> depolarization
82
Purines (ATP, ADP, Adenosine): Metabotropic Receptors - P2Y
- Ligands: ATP, ADP, UTP, UDP - Gs (leads to increase in cAMP) / Gq (leads to production of IP3/DAG --> increase Ca++ release from intracellular stores) coupled
83
Purines (ATP, ADP, Adenosine): Metabotropic Receptors - P1(A)
- Ligand: Adenosine - Post-synpatic locations -- involved in sleep induction in hypothalamus and general inhibition of neural function - Pre-synaptic locations -- involed in inhibition of NT release via negative feedback loop

NE Exam 2 (19 decks)

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