Chemical Msngr & Excitotoxicity Karius T#2 Flashcards

1
Q

Where are serotonergic nerurons found?

A

Raphe nuclei

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2
Q

What are the five monoamines?

A
  1. epinephrine
  2. norepinephrine
  3. dopamine
  4. serotonoin
  5. histamine
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3
Q

Where is Norepinephrine found, what is its role, & how is it made?

A
  • Locus ceruleus, other pontine and medullary areas
  • Plays a role in wakefulness and alertness
  • Derived from Tyrosine- moved into vesicles where it is made
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4
Q

Where is epinephrine found, what is its role, & how is it made?

A
  • Found in medulla
  • Modulatory role
  • Derived from tyrosine which makes dopamine, then NE, from here Epi is made.
    • NE is made in vesicles and neurons have PNMT that convert NE to epi after it leaves the vesicles.
    • Epi is then moved back into the vesicles
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5
Q

How is epi and NE moved into vesicles and what drug targets this?

A
  • VMAT1 and VMAT2
  • Reserpine inhibits this leading to synaptic failure
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6
Q

How is th action of epi and NE limited?

A
  • Reuptake where they are degraded with MAO
  • Enzyme degradation with MAO
  • COMT also degrades
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7
Q

What do NE and Epi bind to?

A
  • alpha adrenergic

beta adrenergic

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8
Q

Where do you find dopamine, how is it made, how is it limited, what are its receptors?

A
  • Basal ganglia for motor control and hypothalamus & limbic system for endocrine and emotional control. Also cortex
  • Made from tyrosine using tyrosine hydroxylase (RLS)
  • Reuptake and catabolism by MAO and COMT
    *
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9
Q

What are dopamines receptors?

A
  • Metabotropic (Serpentine) receptors
  • GPCR’s
    • D1 and D5 increase cAMP using Gs
    • D2 decrease cAMP and increase potassiium efflux
    • D3 and D4 decrease cAMP using Gi
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10
Q

Where do you find 5HT, what is it, how is it made, how is it limited?

A
  • Brainstem Raphe nuclei for modification of motor and sensory actiity. Hypothalamus and limbic system for mood and cerebellum for mods of motor activities.
  • Serotonin
  • Derived from trp using trp hydroxylase
  • Reuptake and catabolism by MAO and COMT
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11
Q

What are serotonin’s receptors?

A
  • 7 receptors with mutliple subtypes
    • Serepentine receptors
  • One Ionotropic receptor 5HT3 for sodium influx
  • 5HT3 is in area postrema for vomiting
  • 5HT6 has an anti-depressant effect
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12
Q

Where do you find histamine, what is its role, how is it made, how is it limited?

A
  • Tuberomammillary nucleus of hypothalamus
  • Wakefulness
  • Derived from histidine using his decarboxylase
  • limited with reuptake and DAO and COMT
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13
Q

What are histamines receptors?

A
  • Serpentine receptors
    • H1: PLC activation
    • H2: increase campt
    • H3: presynaptic decrease histamine release
  • H1 involved with wakefulness
  • More H1 and H3 in the brain than H2
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14
Q

What are the two major inhibitory amino acids?

A
  • GABA
  • Glycine
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15
Q

Where is GABA found?

A
  • Cortex
  • cerebellum
  • basal ganglia
  • amounts start very small at spinal cord and increase as you move superior
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16
Q

What is GABA critical for?

A
  • Consciousness
  • motor control
  • vision
17
Q

How is GABA made and transported?

A
  • From glutamate using glutamate decarboxylase
  • It is transported into vesicles by VGAT
  • Removed from the synapse with GAT
    • GAT1 is on presynaptic terminal
    • GAT2 is on glial cells around the synapse
18
Q

Describe the process GABA goes through if GAT2 takes it up.

A
  1. GAT2 is located on the glial cells and converts it to glutamine
  2. Glutamine is released back out into the ECF
  3. Gln is taken up by presyynaptic terminal and recycled back into GABA
19
Q

What are GABA’s receptors?

A
  • Ionotropic (cl conductance- hyperpolarizes) activation produces IPSP in neurons
  • Multiple bindnig sites such as:
    • Benzodiazepine
    • Ethanol
    • Certain steroides
  • Metabotropic both Gi and Go to activate K channel and inhibit Ca channel
    • Found pre synaptic to regulate NT relase
    • Found post synaptic to inihbit post syn cell
20
Q

Where is glycine found, what is its function, how is it made, how is it r emoved?

A
  • Spinal cord (major)
  • brainstem (medulla)
  • small amounts in higher levels of CNS
  • mediates spinal inhibitions
  • unmodified aa
  • GAT proteins same as GABA remove it
21
Q

What is glycines receptors?

A
  • Ionotropic for chloride
  • influx of Cl leads to ipsp
  • Ethanol and general aneesthethics bind and potentiate it
  • Strychine nbinds and blocks (rat poision)
22
Q

Where are the purines found?

A
  • Basically everywhere in CNS but know cortex cerebellum hippocampus and basal ganglia
23
Q

What are the opoid Mu receptors? What does their activation cause?

A
  • Metobotropic receptors
  • Analgesia
  • Respiratory depression
  • Euphoria
  • Constipation
  • Sedation

leads to increaSae in potassium efflux and hyperpolarization

24
Q

Purine receptors?

A
  • P1 (A receptors): ligand is adenosine, post synaptic location induce sleep and inhibit neural function. Presynaptic locations inhibit NT release
  • P2 receptors: learnign and memory co release with EAA’s and movdification of locomotor paths
    • P2X: ionotropic ATP is ligand
    • P2Y: Metabotropic ligand is ATP ADP UTP UDP Gi/Gq coupled
25
Q

The endorphins include what four peptide families?

A
  • Endorphins
  • Enkephalins
  • Dynorphins
  • Nociceptin
26
Q

Where are opoids found?

A
  • Basal ganglia
  • Hypothalamus
  • Multiple pontien and medullary sites
27
Q

Genreal functions of opoids?

A

Modification of nociceptive inputss

Mood modification

28
Q

What are the four precursor molecules to the opoids?

A
  • Proopiiomelanocortinin (POMC): percursor to ACTH and B-endorphins
  • Pro-enkephalin
    • Tyr-Gly-Gly-Phe- X (X=Met or Leu)
  • Pro-dynorphin: 3 molecules of Leu-Enkephalin
  • Orphainin FQ: Nociceptin
29
Q

How are opoids removed?

A
  • Probable reuptake
  • Enzymatic destruction via enkephalinase and aminopeptidase
30
Q

What are the opoid Kappa receptors? Activation causes ____?

A
  • Serpentine receptors
  • Produces analgesia
  • dysphoria
  • diuresis
  • miosis

Decrease calcium influx

31
Q

What does the delta opoid receptor cause and what is it?

A
  • Serpentine receptor
  • Causes analgesia when activated

Decrease calcium influx

32
Q

What do all opoid receptors have in common?

A
  • ALL are metabotropic/serpentine
  • ALL connect to Gi/Go