3 - Neurotransmitters Flashcards

1
Q

Classification of Neurotransmitters

A
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2
Q

Selected Neuropeptide Transmitters

A
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3
Q

List the neurotransmitters in the classifical classification

A

Acetylcholine

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4
Q

List the neurotransmitters that are monoamines

A

Epinephrine
Norepinephrine
Dopamine
Serotonin
Histamine

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5
Q

list the neurotransmitters that are amino acids

A

GABA (𝛾-aminobutyric acid)
Glycine
Glutamate and Aspartate

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6
Q

List the neurotransmitters that are soluble gases

A

nitric oxide (NO)
carbon monoxide (CO)

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7
Q

list neurotransmitters that are lipids (endocannabinoids)

A

Anandamide

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8
Q

List the large molecule neuropeptide families

A

hypothalamic peptides
pituitary peptide hormones
brain-gut peptides
brain-endocrine peptides
brain-skin peptides
Trophic factors

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9
Q

Neuropeptide Transmitters - list the hypothalamic releasing hormones

A

thyrotropin releasing hormone
luteinizing hormone releasing
somatostatin

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10
Q

Neuropeptide Transmitters - list the pituitary peptides

A

adrenocorticotropic hormone
Ξ²-endorphin
⍺-melanocyte stimulating hormone
prolactin
luteinizing hormone
growth hormone
oxytocin
vasopressin
thyrotropin

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11
Q

Neuropeptide Transmitters - List the Gut-Brain Peptides

A

Leu-, Met-Enkephalin
Substance P
Gastrin
Cholecystakinin
Vasoactive intestinal polypeptide
Insulin
Glucagon
Neurotensin

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12
Q

Neuropeptide Transmitters - list the Growth Factors

A

Nerve growth factor
Brain-derived neurotropic factor

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13
Q

Neuropeptide Transmitters - others

A

bradykinin
Angiotensin II
Calcitonin

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14
Q

Steps in Neurochemical Transmission (know this down cold)

A
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15
Q

Acetylcholine

A
  • First neurotransmitter discovered
  • Released by all preganglionic neurons of autonomic nervous system and postganglionic parasympathetic neurons
  • Released at neuromuscular junction
  • Many brain pathways
  • Many pharmacological agents interact with acetylcholine receptors
  • Role in cognitive function
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16
Q

Acetylcholine synthesis

A
  • Precursors
    -Acetyl-CoA from Kreb cycle activity
    -Choline from the diet β†’ lecithin is a good dietary source of choline
  • Primary synthetic Enzyme
    -choline acetyltransferase
  • Rate-limiting step of synthesis is Choline uptake into the presynaptic terminal
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17
Q

Presynaptic Cholinergic Neuron

A

functions in storage and release of neurotransmitters
* Storage
-Vesicular acetylcholine transporter (VAT)
-active transport
-counter ions (ATP)
* Release
-Involves vesicle docking and fusion with cell membrane
-calcium dependent
-Botulinum toxin sensitive→specific presynaptic ganglioside

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18
Q

Acetylcholine inactivation

A
  • Acetylcholinesterase (AChE)
    – Bound to post-synaptic membrane
    – Mediates hydrolysis of acetylcholine to choline and acetate
    – High catalytic activity
    – Primary target of nerve gas agents and organophosphate pesticides (they inhibit AChE)
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19
Q

Acetylcholine Receptors

A
  • Nicotinic
    – Ligand-gated cation channels
    – Heterologous pentamers
    β†’ Subunit families: ⍺1-⍺10, Ξ²2-Ξ²5, Delta, Epsilon, Gamma
    – Neuromuscular junction
    β†’ Subtype N1 (Nm)
    – Autonomic ganglia, adrenal medulla and brain
    β†’ N2 (N_N) subtype
  • Muscarinic
    – G-protein-linked
    – Single subunit or dimer of two subunits
    – Subtypes: M1-M5
    – Peripheral end-organs innervated by the parasympathetic nervous system
    – Wide distribution in the brain
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20
Q

Central Cholinergic Pathways

A
  • Basal forebrain to cortex and cingulate gyrus
    – Cognition, attention
    – Dementia therapy
  • Septo-hippocampal
    – Memory
    – Dementia therapy
  • Brainstem projections
    – Autonomic functions
  • Striatal interneurons
    – Motor system
    – Extrapyramidal
    – Parkinson’s therapy
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21
Q

GABA (Gamma - Aminobutyric Acid)

A
  • The primary inhibitory transmitter in the nervous system
  • Inhibitory electrophysiological effects are produced by increasing membrane chloride influx through GABA-A receptors
  • Along with glutamate (which is excitatory), it regulates the overall tone of nervous system activity
  • It is implicated in etiology of many brain diseases including Huntington disease, epilepsy, alcoholism, depression
  • Mediates the effects of most central nervous system depressant drugs
22
Q

GABA Synthesis

A
  • Kreb cycle shunt pathway
  • Precursor
    – Glutamate
  • Rate-limiting enzyme
    – Glutamic acid decarboxylase (GAD)
  • GAD isoforms
    – GAD65, GAD67
  • Enzyme co-factor
    – Pyridoxal phosphate (vitamin B6)
    – B6 deficiency may present with seizures
23
Q

GABA Storage and Release

A
  • Storage
    – Active transport into synaptic vesicles
    – Vesicular GABA transporter (VGAT)
  • Release
    – Vesicular, calcium-dependent
    – Non-vesicular, calcium-independent
    β†’ Involves reversal of presynaptic uptake protein function
24
Q

GABA Inactivation

A
  • Reuptake by presynaptic neuronal transporters
    – Re-packaged in synaptic vesicles
  • Reuptake by glial transporters
    – Enzymatic degradation
    – Several key metabolic enzymes involved
25
Q

GABA Metabolism

A
  • Enzymatic degradation
    – GABA Transaminase (GABA-T)
  • Converts GABA to succinic semi-aldehyde (SSA)
  • SSA converted to succinate by SSA dehydrogenase
26
Q

GABA Receptors

A
  • GABA-A
    – Ligand-gated chloride channel
    – Heterologous pentamer
    – Subunit families
  • a1-6, b1-4, g1-4, d1-2, t1, e1, r1-3
    – Mediates β€œfast” inhibitory transmission (millisecond time course)
  • GABA-B
    – G-protein-linked
    – Heterologous dimer
  • GABR1, GABR2
    – Mediates β€œslow” inhibitory
    transmission
    – Variably long time course
27
Q

GABA-A Receptor Function

A
  • GABA-A activation causes neuronal inhibition
    – Depresses activity of the CNS
  • Agonists are used for
    – Insomnia
    – Anxiety
    – Epilepsy
    – General anesthesia
28
Q

Major GABA Pathways

A
  • Projection pathways
    – Hippocampus
    β†’ Basket cells, stellate cells
    – Cerebellum
    β†’ Purkinje cells, Golgi cells
    – Striatonigral, pallidonigral
    β†’ Neurons in striatum and globus pallidus project to substantia nigra (Huntington disease)
    – Thalamocortical
    β†’ Thalamic nuclei project to
    neocortex (Absence epilepsy)
  • Interneurons
    – Ubiquitous including neocortex, basal ganglia, cerebellum, spinal cord
29
Q

Glutamate

A
  • The primary excitatory transmitter in the nervous system
  • Excitatory electrophysiological effects via increased cation conductance through activated glutamate receptors
  • Along with GABA (which is inhibitory), it regulates the overall tone of nervous system activity
  • Glutamate and related excitatory amino acids (EAAs) implicated in etiology of many neurological and psychiatric diseases including schizophrenia, epilepsy, stroke and neurodegenerative illnesses
  • Small but growing number of clinically relevant pharmacologic agents target glutamatergic neurons
30
Q

Glutamate Synthesis

A
  • Aminotransferase
    – Expressed in all cells
  • Krebs cycle enzyme
    – Uses vitamin B6 as co-factor
  • Glutamine synthetase
    – Expressed only in glia
    – Uses ATP as a co-factor
  • Glutaminase
    – Expressed only in neurons
31
Q

Glutamate Neurochemistry

A
32
Q

Glutamate Receptors

A
33
Q

Glutamate Receptor Function

A
34
Q

Major Glutamate Pathways

A
35
Q

Brain Monoamines

A
36
Q

Catecholamine Synthesis

A
37
Q

Catecholamine Neurochemistry

A
38
Q

Dopamine Receptors

A
39
Q

Major Dopamine Pathways

A
40
Q

Major Dopamine Functions

A
41
Q

Norepinephrine Receptors

A
42
Q

Major Norepinephrine Pathways

A
43
Q

Major Norepinephrine Functions

A
44
Q

Serotonin Neurochemistry

A
45
Q

Serotonin Receptors

A
46
Q

Major Serotonin Pathways

A
47
Q

Major Serotonin Functions

A
48
Q

Endogenous Opioid Neuropeptides

A
49
Q

Major Opioid Receptors

A
50
Q

Neurotransmitter Colocalization

A
51
Q

Neurotransmitter Colocalization

A
52
Q

Neurotransmitters summary

A