19: Neurotransmitters Flashcards
Glutamate and aspartate: nt vs AA
Metabolic and transmitter pools are kept strictly separate
What does NMDA stand for?
N-methyl-D-aspartate
Is NMDA ligand or voltage gated?
Both - Mg makes it ligand gated
Epsp of NMDA receptor vs non-NMDA
NMDA: longer latency and duration
Non-NMDA: relatively short onset and duration
Two types of non-NMDA receptors
AMPA, Kainate
Kainate receptor
Allows some Ca influx as well
Modulatory site on AMPA receptor
For benzos, decreases amount of Na that can enter
What happens in areas where there are both NMDA and non-NMDA receptors?
- EAA binds both receptor types, opening both channels
- Na flows in non-NMDA channels, but is blocked from NMDA by Mg
- Epsp from non-NMDA -> depol
- Mg leaves due to depol
- Ca can enter NMDA -> longer lasting epsp
EAAs in high doses
Cause damage/toxicity
EAA uptake by glial cells
In glial cell, turns into glutamine, is released back into synaptic cleft for Reuptake and recycling by pre-synaptic cell
Does EAA uptake by glial cells require energy?
Yes, requires ATP
What happens when Ca enters a cell via NMDA receptor?
Activates calcineurin -> activates NOS -> forms NO
Which cell types can NO act on?
Pre and post synaptic - its lipid soluble so it diffuses through synaptic cleft
NO functions
Memory, CV and respiratory control, immunologic fxs, potent vasodilator
Downside of NO
Very unstable with a 5 second half life, produces free radicals
monoamine class
All nts created by modifying a single AA
Rate limiting step of Tyrosine -> epi
Tyrosine -> L-dopa via tyrosine hydroxylase
What enzyme converts norep to epi
PNMT
VMAT1 and 2
Vesicular monoamine transporters to move epi into vesicles
Reserpine
Inhibits VMAT 1 and 2
MAO
Monoamine oxidase, on mito surface
COMT
Catechol-o-methyl transferase
Polymorphisms in COMT
Increased risk of depression and anxiety
What does 5HT stand for
5-hydroxy-tryptophan
DAO
Diamine oxidase
What does GABA stand for
y-amino butyric acid
Protein that moves GABA into vesicles and those that remove GABA from synapse
VGAT: into vesicles
GAT: removed from synapse
GAT1 vs GAT2 location
GAT1: presynaptic terminal
GAT2: glial cells around synapse
What happens if GAT2 takes up GABA
Converted to glutamine and released into ECF for recycling
Benzos, EtOH, and steroid affect on GABA A receptors
Potentiate its action -> bigger ipsp’s
Extra-synaptic GABA A receptors
Possible site of action for many general anesthetics, like propofol
Pre- vs post synaptic GABA B receptors
Pre: regulates nt release
Post: inhibits post-synaptic cell
What do ethanol, general anesthetics, and strychnine do to glycine receptor?
Ethanol and general anesthetics: potentiate
Strychnine: blocks it
What protein stores ATP into vesicles
VNUT
Where does ATP break down into ADP and then adenosine?
In synaptic cleft
What does the word endorphins come form
Endogenous morphines
Examples of peptide transmitters
Opioids, tachykinins, cholecystokinin, somatostatin
What does pro-opiomelanocorinin form?
B-endorphins
Formation of all peptide nts, including opioids
Standard protein synthesis in soma, transported down axon via fast axonal transport
What are endocannabinoids derived from?
Membrane lipid arachidonic acid
What is a major source of arachidonic acid in the brain?
2AG
Where are CB1s located?
CNS neurons, largely presynaptic of neurons that release EAA and GABA
Which receptor has 99% homologs with rat version, and is likely a critical receptor
CB1
Polymorphisms in CB1
Obesity, ADHD, schizophrenia, depression, Parkinson’s
FAAH
FA amide hydrolase, breaks down anandamide
MAGL
Mono-acyl glycerol lipase, breaks down 2AG
Two enzymes that oxidize/break down endocannabinoids
Cyclo-oxygenase, lipoxygenase
