Chemical Msngr & Excitotoxicity Karius T#2 Flashcards
Where are serotonergic nerurons found?
Raphe nuclei
What are the five monoamines?
- epinephrine
- norepinephrine
- dopamine
- serotonoin
- histamine
Where is Norepinephrine found, what is its role, & how is it made?
- Locus ceruleus, other pontine and medullary areas
- Plays a role in wakefulness and alertness
- Derived from Tyrosine- moved into vesicles where it is made
Where is epinephrine found, what is its role, & how is it made?
- 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
How is epi and NE moved into vesicles and what drug targets this?
- VMAT1 and VMAT2
- Reserpine inhibits this leading to synaptic failure
How is th action of epi and NE limited?
- Reuptake where they are degraded with MAO
- Enzyme degradation with MAO
- COMT also degrades
What do NE and Epi bind to?
- alpha adrenergic
beta adrenergic
Where do you find dopamine, how is it made, how is it limited, what are its receptors?
- 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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What are dopamines receptors?
- 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
Where do you find 5HT, what is it, how is it made, how is it limited?
- 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
What are serotonin’s receptors?
- 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
Where do you find histamine, what is its role, how is it made, how is it limited?
- Tuberomammillary nucleus of hypothalamus
- Wakefulness
- Derived from histidine using his decarboxylase
- limited with reuptake and DAO and COMT
What are histamines receptors?
- 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
What are the two major inhibitory amino acids?
- GABA
- Glycine
Where is GABA found?
- Cortex
- cerebellum
- basal ganglia
- amounts start very small at spinal cord and increase as you move superior
What is GABA critical for?
- Consciousness
- motor control
- vision
How is GABA made and transported?
- 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
Describe the process GABA goes through if GAT2 takes it up.
- GAT2 is located on the glial cells and converts it to glutamine
- Glutamine is released back out into the ECF
- Gln is taken up by presyynaptic terminal and recycled back into GABA
What are GABA’s receptors?
- 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
Where is glycine found, what is its function, how is it made, how is it r emoved?
- Spinal cord (major)
- brainstem (medulla)
- small amounts in higher levels of CNS
- mediates spinal inhibitions
- unmodified aa
- GAT proteins same as GABA remove it
What is glycines receptors?
- Ionotropic for chloride
- influx of Cl leads to ipsp
- Ethanol and general aneesthethics bind and potentiate it
- Strychine nbinds and blocks (rat poision)
Where are the purines found?
- Basically everywhere in CNS but know cortex cerebellum hippocampus and basal ganglia
What are the opoid Mu receptors? What does their activation cause?
- Metobotropic receptors
- Analgesia
- Respiratory depression
- Euphoria
- Constipation
- Sedation
leads to increaSae in potassium efflux and hyperpolarization
Purine receptors?
- 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
