Neurotransmitter Systems Flashcards
Ach - General function
Crucial in producing consciousness, but not awareness
control of voluntary motion
initiation of REM sleep
Ach - central locations
pons
midbrain
the striatum
Ach - vesicular storage
Ach stored in clear vesicles
Moved into vesicles by VAchT
Ach - Catabolism
Acetylcholinesterase bound to the POST synaptic cell membrane
Ach Receptors (2)
nicotinic (NAchR)
muscarinic (MAchR)
Muscarinic receptor properties
4 or 5 different types, all activated by muscarine
serpentine receptor
GPCR
M1 (neuronal) MAchR
Gq
increase IP3/DAG, Increase Ca++
M2 (cardiac) MAchR
Gi
decrease cAMP, increase K+ efflux
M3 (sm m. of bronchi, vasculature, endothelial cells of vasculature) MAchR
NO
Gq
IP3/DAG, increase Ca++
in the vasculature NO is the major effector (which wins)
Nicotinic receptors
located at NMJ (Na), autonomic ganglia, other parts of the CNS (Ca, Na)
5 subunits
IONOTROPIC
allow for Na entrance, allthough some neuronal forms allow for significant Ca influx
Amino acid NTs (list)
glutamate, aspartate, taurine (EAAS)
GABA, glycine (inhibitory amino acids)
GABA - location
cerebellum
cortex
retina
GABA - functional roles
major inhibitory NT in the higher CNS
critical for producing consciousness/awareness
control of voluntary motion
GABA - synthesis
glutamate decarboxylase (GAD) derived from glutamate
GABA - how is action limited
reuptake
catabolism by GABA transaminase
GABA - what does it bind to
GABA-A and GABA-B receptors
GABA-A receptors ionotropic/metabotropic subunits ion conductance (if ionotropic)/Gprotein if metabotropic other important chemicals
IONOTROPIC
5 subunits
Cl- conductance
benzodiazapine site potentiates
GABA-B receptors ionotropic/metabotropic subunits ion conductance (if ionotropic)/Gprotein if metabotropic other important chemicals
heterodimer G protein (Gq and Gi) decreases adenylyl cyclase, increases K+ efflux. AND decreases IP3/DAG, decreases Ca influx
-
Many general anesthetics are now postulated to produce anesthesia by activating what receptors?
GABA receptors, mostly GABA-A, at extra-synaptic locations throughout the cortex
Glycine - location
spinal cord
brainstem
forebrain (less than gaba)
glycine - function
mediates many spinal inhibitions
glycine - binds to
glycine receptors
glycine receptor ionotropic/metabotropic subunits ion conductance (if ionotropic)/Gprotein if metabotropic other important chemicals
ionotropic
a=glycine binding, b = structural
Cl-
blocked by strychnine
Peptide NT (2)
opiods
endocannabanoids
coded for by genes, originally thought to be neuromodulators
Opiods - location
basal ganglia
hypothalamus
parabrachial nuclei and raphe nuclei
opiods - general functions
modification of nociceptive inputs
modification of mood/affect
Opioid - 4 precursor molecules
proenkephalin
pro-opiomelanocortin
prodynorphin
orphanin FQ
proenkephalin - sequence and 2 major variants
tyr-gly-gly-phe-x
met-enkephalin
leu-enkephalin
pro-opiomelanocortin (POMC)
B endorphins
prodynorphin
When you cut up prodynophin, it gives rise to 4 opioid molecules
3 molecules of leu-enkephalin
dynorphins (8aa or 17aa) –> a smaller form OR the larger form
Orphanin FQ aka?
nociceptin
How are opioids made?
Since they are peptides, they are made through the usual protein synthetic machinery
How do we limit opioid action?
enzymatic activity, possibly after reuptake
enkephalinase A and B
aminopeptidase
What (3) receptors do opioids bind to?
mu, kappa, delta
Mu receptor
receptor type and effects
serpentine
ANALGESIA, RESPIRATORY DEPRESSION, EUPHORIA
sedation, constipation
Kappa receptor
receptor type and effects
serpentine receptor,
ANALGESIA, DYSPHORIA
diuresis, miosis
Delta receptor
receptor type and effects
serpentine
ANALGESIA
all opioid receptors are _______ and are ______ adenylyl cyclase
serpentine receptors
inhibit
Mu - increases K+ efflux and hyperpolarizes
Kappa and delta - decrease Ca
The two endocannabanoids are
anadaminde
2-AG (arachydonylglycerol)
Anadamide
“bliss”
arachidonic acid +ethanoloamine
2-Arachydonylglycerol
arachadonic acid esterified into the middle, #2 position of glycerol
Distribution of endocannabinoids in the CNS
broad distribution hippocampus - memory formation Basal Ganglia - affect, motor spinal cord - modulation of nociception neocortex - neuroprotective (?)
What type of receptors do the endocannabinoids bind to? (2)
CB-1 and CB-2
CB-1 receptor where what type what it does what it binds
axons and presynaptic terminals of EAA and GABA synapses
Gi protein coupled receptor
reduces NT release
binds to either anadamide or 2-AG equally
CB -2 receptor where what type of receptor additional sites found function
found in brain MICROGLIA, not neurons
metabotropic
immune system and gut
antiinflammatory, in brain cause macrophage to remove B-amyloid
