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Flashcards in Neurotransmitter Systems Deck (83)
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1
Q

What are the 5 monoamines?

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

Norepinephrine: Location

A
  • Locus Ceruleus
  • Medulla
3
Q

Norepinephrine: Functions

A

Wakefulness/Arousal

4
Q

Norepinephrine: Ionotropic Receptors

A

NA

5
Q

Norepinephrine: Metabotropic Receptors

A
  • Alpha-Adrenergic
  • Beta-Adrenergic
6
Q

What is Norepinephrine derieved from?

A

Tyrosine

7
Q

Epinephrine: Location

A

Medulla

8
Q

Epinephrine: Function

A

Modulatory

9
Q

Epinephrine: Ionotropic Receptors

A

NA

10
Q

Epinephrine: Metabotropic Receptors

A
  • Alpha-Adrenergic
  • Beta-Adrenergic
11
Q

What is Epinephrine derived from?

A

Tyrosine

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

13
Q

Proteins that move Epinephrine into vesicles:

A

Vesicular MonoAmine Transport Proteins – VMAT1 and VMAT2

14
Q

Reserpine

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

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

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

Monoamine Oxidase

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

18
Q

Serpentine Receptors

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

Dopamine: Location

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

Role of Dopamine in Basal Ganglia:

A

Motor control

21
Q

Role of Dopamine in Hypothalamus and Limbic System:

A

Endocrine and emotional control

22
Q

Dopamine: Functions

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

Dopamine: Ionotropic Receptors

A

NA

24
Q

Dopamine: Metabotropic Receptors

A
  • D1
  • D2
  • D3
  • D4
  • D5
25
Q

Dopamine: D1 and D5 Receptors

A
  • Connected to Gs protein
  • Increase cAMP (via increased adenylate cyclase activity)
26
Q

Dopamine: D2 Receptors

A
  • Connected to Gi protein
  • Decrease in cAMP (via decreased adenylate cyclase activity) –> increased Potassium Efflux (creates hyperpolarization of the cell)
27
Q

Dopamine: D3 and D4 Receptors

A
  • Connected to Gi protein
  • Leads to decreased cAMP (via decreased adenylate cyclase activity)
28
Q

Serotonin: Location

A
  • Hypothalamus
  • Limbic System
  • Cerebellum
  • Raphe Nuclei (located in brainstem)
29
Q

Role of Serotonin in Hypothalamus and Limbic System:

A

Mood

30
Q

Role of Serotonin in Raphe Nuclei:

A

Modification of motor and sensory activity

31
Q

Role of Serotonin in Cerebellum:

A

Modification of motor activity

32
Q

What is Serotonin derived from?

A

Tryptophan
(via Tryptophan Hydroxylase enzyme)

33
Q

Serotonin: Functions

A
  • Mood and affect
  • Arousal
  • Modification of sensory and motor inputs
34
Q

Serotonin: Ionotropic Receptors

A

5HT3 (Na+ influx)

35
Q

Serotonin: Metabotropic Receptors

A
  • 5HT1
  • 5HT2
  • 5HT4
  • 5HT5
  • 5HT6
36
Q

What happens if 5HT3 is activated in the Area Postrema?

A

Vomiting

37
Q

What is the effect of Serotonin binding to 5HT6?

A

Ani-depressant effect

38
Q

Histamine: Location

A

Hypothalamus — specifically the Tuberomammillary Nucleus

39
Q

Histamine: Functions

A

Arousal

40
Q

Histamine: Ionotropic Receptors

A

NA

41
Q

Histamine: Metabotropic Receptors

A
  • H1
  • H2
  • H3
42
Q

Histamine: H1 Receptor

A
  • Binding leads to PLC activation
  • Involved in wakefulness
  • Largely peripheral
43
Q

Histamine: H2 Receptor

A
  • Binding leads to increase cAMP
  • Associated with gastric acid release
  • Largely peripheral
44
Q

Histamine: H3 Receptor

A
  • Presynaptic receptor
  • Binding leads to decreased histamine release – part of feedback system; tells cell ‘you have released enough histamine and can stop now’
45
Q

Acetylcholine: Location

A
  • Pons and Midbrain
  • Striatum (Caudate + Putamen) of Basal Ganglia
46
Q

Acetylcholine Function in the Striatum

A

Control of voluntary motion

47
Q

Acetylcholine Function in the Midbrain and Pons

A
  • Baseline excitation to cortex (brain arousal mechanisms)
  • REM sleep
48
Q

Acetylcholine: Function

A
  • Wakefulness
  • Motor Control
49
Q

Acetylcholine: Ionotropic Receptors

A

Nicotinic

50
Q

Acetylcholine: Location of Nicotinic Receptors

A
  • Thalamus
  • Cortex (diffusely)
51
Q

Acetylcholine: Nicotinic Receptors

A
  • 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
Q

Acetylcholine: Synthesis

A
  • 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
Q

Acetylcholine: Metabotropic Receptors

A
  • 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
Q

Acetylcholine: Notes

A

Different from the ACh found in the NMJ and ANS

55
Q

Two major inhibitory amino acids:

A

(1) GABA
(2) Glycine

56
Q

What is the major inhibitory AA NT found in the CNS?

A

GABA

57
Q

Location in CNS that contains the lease amount of GABA:

A

Spinal Cord

58
Q

GABA: Central Location

A

Higher CNS
- Cortex
- Cerebellum
- Basal Ganglia

59
Q

GABA: Critical Functions

A
  • Consciousness
  • Motor Control
  • Vision (retina)
60
Q

GABA: Ionotropic Receptors

A

GABA(A)

61
Q

GABA: Synthesis

A
  • Glutamate –> GABA via Glutamate Decarboxylase (GAD)
  • Transported into vesicels by Vesicular GABA Transporter Protein (VGAT)
  • Removed from synapses via GAT (GABA Transporter)
62
Q

GABA: GAT

A
  • GAT1: located on presynaptic terminal, involved in reuptake
  • GAT2: located on glial cells surrounding the synapse, involved in reuptake and further modification
63
Q

GABA: GAT1

A
  • Takes GABA back up into presynaptic Terminal
  • Repackages GABA into vesicles as is
64
Q

GABA: GAT2

A
  • 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
Q

GABA: Ionotropic Receptors - GABA(A)

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
Q

There are many ___-____ GABA(A) receptors

A

Extra-synaptic

(believe these receptors are the site of action for many general anesthetics including Propofol – hyperpolarize the cell until you lose consciousness)

67
Q

GABA: Metabotropic Receptors

A

GABA(B)

68
Q

GABA: Metabotropic Receptors - GABA(B)

A
  • 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
Q

Glycine: Location

A
  • Spinal Cord
  • Lower CNS
70
Q

Glycine: Function

A

General inhibition

71
Q

Glycine: Ionotropic Receptors

A

GlyR

72
Q

Glycine: Metabotropic Receptors

A

None

73
Q

Glycine: Ionotropic Receptors - GlyR

A
  • 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
Q

Purines (ATP, ADP, Adenosine): Location

A

Widespread (cortex, cerebellum, hippocampus, basal ganglia, hypothalamus)

75
Q

Purines (Adenosine): Function

A
  • Sleep
  • Inhibition
76
Q

Purines (ATP): Functions

A

Multiple – found in every NT vesicle in presynaptic terminal

77
Q

Purines (ATP, ADP, Adenosine): Synthesis

A
  • ATP by mitochondria (presyn terminal has many mitochondria)
  • Stored in vesicles (VNUT protein)
  • Released
  • ATP –> ADP –> Adenosine; occurs in synaptic trough
78
Q

Purines (ATP, ADP, Adenosine): Ionotropic Receptors

A

P2X

79
Q

Purines (ATP, ADP, Adenosine): Metabotropic Receptors

A
  • P1(A)
  • P2Y
80
Q

Purines (ATP, ADP, Adenosine): P2 (P2X, P2Y) Receptor Functions

A
  • Learning and memory
    (co-release with EAA)
  • Modification of locomotor pathways
81
Q

Purines (ATP, ADP, Adenosine): Ionotropic Receptors - P2X

A
  • Ligand: ATP
  • Many subtypes
  • Binding of ATP leads to influx of Na+ and Ca++ into the neuron –> depolarization
82
Q

Purines (ATP, ADP, Adenosine): Metabotropic Receptors - P2Y

A
  • 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
Q

Purines (ATP, ADP, Adenosine): Metabotropic Receptors - P1(A)

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