Neurotransmitters Flashcards
What are the Monoamines
neurotransmitters created by modifying a single amino acid
Epinephrine Norepinephrine dopamine serotonin histamine
Where is norepinephrine made
Locus ceruleus
other pontine/medullary areas
Wakefulness/alertness
WHere is Epinephrine made
Medulla
How is Epinephrine and norepinephrine made
Derived from tyrosine
tyrosine is converted to dopamine which is converted to norepi then to epi
Tyrosine hydoxylase conversion of tyrosine to DOPA is the rate limiting step
Dopa is moved into vesicles where NE is created and then Phenolethanolamine N Methyl transferase converts the NE to the Epi
What inhibits the movement of Epi and NE being moved into vesicles by VMAT1 and VMAT2
Reserpine
How is the action of Epi and Ne limited
Reuptake
Enzymatic degradation via monoamine oxidase and Catechol-O-methyltransferase
What do Epinephrine and Norepinephrine bind too
alpha and beta adrenergic receptors
serpentine receptors
Where do you find dopamine
Basal ganglia
hypothalamus and limbic system
cortex
How is dopamine made
precursor to epinephrine made from tyrosine via tyrosine hydroxylase
What does dopamine bind to
5 receptor types which are serpentine receptors
D1 and D5: increase cAMP
D2: decrease cAMP and increase potassium efflex
D3 and D4: decrease cAMP
WHere do you find serotonin
Hypothalamus and limbic system
Cerebellum
Raphe nuclei
How do you make serotonin
derived from tryptophan via tryptophan hydroxylase
How do you limit Serotonin
reuptake
Enzymatic degradation via monoamine oxidase and Catechol-O-methyltransferase
what are the receptors of serotonin
7 receptors, 6 are serpentine receptors, and one is ionotropic
5HT3 (ionotropic) does Na influx in the area postrema (vomiting)
5HT6: antidepressant effect
Where do we find histamine
Tuberomammillary nucleus of the thalamus
How do you make histamine
derived from histidine via histidine decarboxylase
How do you limit histamines action
reuptake
Enzymatic degradation via diamine oxidase and Catechol-O-methyltransferase
Whate are the receptors of histamine
3 serpentine receptors
H1: PLC activation
H2: increase cAMP
H3: presynaptic, decrease histamine release
H1 involved in wakefulness
Where are neurons that make acetylcholine
The striatum of basal ganglia: caudate and putamen
these can be found in the midbrain and the pons
How is acetylcholine made and broken down
Synthesis of choline and acetate
moved into vesicles via Vesicular Ach Transporter protein (VAchT)
then removed from synapse via acetylcholinesterase
What are the receptors of Aceytylcholine: muscarinic
5 muscarinic receptors
Serpentine/metabotropic
M1: neuronal, and increases Ca++
M4: presynaptic autoreceptor, striatum of basal ganglia: decrease cAMP
M5: cerebrovasculature; dopaminergic neurons of basal ganglia: increase IP3/DAG
What are the receptors of Acetylcholine nicotinic receptors
located at the NMJ
synapse between pre and post ganglionic cells in autonomic ganglia
various subunits and by changing the subunits changes the properties of the channel and in some central synapses creates a nicotinic channel that allows more calcium in
What is the major role of GABA and where is it found
Major inhibitory amino acids in the CNS
widely distributed throughout the higher levels of the CNS
Spinal cord has least GABA of all locations
What roles is GABA critical in
Consciousness
Motor control
Vision
How is GABA synthesized and removed
synthesis from glutamate via glutamate decarboxylase
Transported into vesicles via Vesicular GABA transporter protein
removed via GAT
- GAT1 is found on the presynaptic terminal
- GAT2 is found on the glial cells surrounding the synapse (GAT2 will also convert GABA to glutamine and release it the ECF where it will be taken to presynaptic cell and reconverted to GABA
GABA a Receptors
Ionotropic (Cl conductance
generates an IPSP
Modulates: Benzodiazepine, ethanol, steroids, general anesthetics like propfol
GABA b receptors
Metabotropic
Gi/Go protein coupled
activate a K+ channel and close down and inhibit Ca++ channel
located:
Presynaptic: regulate NT release
Postsynaptic: inhibition of post synaptic cell
Where is Glycine found and what is its function
Spinal cord
and much less in higher areas of the CNS
Function: mediate many spinal inhibitions
How is glycine produced and removed from the synapse
Produced via unmodified amino acid
romoved from the synapse via the GAT proteins
What is the receptor of glycine, and what blocks this receptor
Ionotropic: Chloride
Influx of chloride leads to ipsp
Ethanol, and general anesthetics also bind to these receptors
Stychnine: binds to it and blocks this glycine receptor
Where are purines found in the CNS
found virtually everywhere in the central nervous system especially: cortex cerebellum hippocampus basal ganglia
P1 receptors of Purines
Ligand: Adenosine
Postsynaptic locations: does sleep induction
general inhibition of neural function
Presynaptic locations: Inhibition of neurotransmitter release
P2 receptors of Purines
P2X: Ionotropic
Ligand: ATP
Manysuptypes
P2Y: Metabotropic
Ligand: ATP, ADP, UTP, UDP
Gi/gq coupled
Functions:
Learning and memory (co release with EAA)
modification of locomotor pathways
What are the 4 peptides included in the peptide family, and what are their general functions
endorphins
enkephalins
dynorphins
nociceptine
Modification of nociceptive inputs (cutaneus senses)
Mood/Affect (Neurophysiology of emotion/drug addiction)
Where are opioids found in the CNS
Basal ganglia
hypothalamus
pontine and medullary sites
What are the 4 pre precursor molecules
Proopiomelanocortinin
Pro-enkephalin
Pro-dynorphin
Orphanin FQ
What is the synthesis and removal of the opioids
synthesis: standard protein synthesis in the cell body
removal from trough/cleft via reuptake
and ezymatic destruction via: enkephalinase and aminopeptidase
What does the Mu receptor do
for opioids
Metobotropic recceptor
Gi/Go
Leads to an increase inpotassium efflux and hyperpolarization
Activation causes: analgesia respiratory depression euphoria constipation sedation
What does the Kappa receptor do
for opioids
Serpentine receptor
Gi/Go
Decreases calcium influx
Produces Analgesia Dysphoria diuresis miosis
What does the Delta receptor do
it is for opioids
decreases Calcium influx
it is a serpentine receptor
Gi/Go
Produces analgesia when activated
What are endocannabinoids
Anandamide
2-Arachidonylglycerol (2AG)
Where are endocannabinoids found in the CNS
Basal ganglia: mood, motor performance
Spinal cord: modulation of nociception
Cortex: neuroprotection
Hippocampus: Memory formation
Hypothalamus: Control of body energy/hunger
What are the synthesis pathways of endogenous cannabinoids
Derived from membrane lipids: Arachidonic acid
Anadamide: Derived from N-arachidonyl phosphatidyl ethanol (NAPE)
2-AG: Derived from arachidonyl-containing phosphatidyl inositol bis phosphate (PIP2)
since 2-AG plays an important role for Arachidonic acid, pharmalogical manipulation of 2-AG production has wide reaching effects beyond those of the endocannabinoid system
Cannabinoid receptor # 1
found in uniform distribution: striatum, thalamus, hypothalamus, cerebellum, lower brainstem
found in non uniform: cortex, amygdala, hippocampus
effects of the Cannabinoid receptor 1
found on pre-synaptic terminals of EAA and GABA releasing synapses
reduces EAA and GABA release
help with neuroprotection/ mood/ nociception
done via Gi coupled protein
Anamide and 2-AG are equally effective
Cannabinoid receptor 2
Initially reported as peripheral receptors found primarily on macrophages
also found on microgila
Highly inducible in response to injury or inflammation
binds 2-AG better than AEA
Degradation of the endocannabinoids at the synapse
2 way pathway:
Hydrolysis
- Anandamide via Fatty acid amide hydrolase
- 2-AG monoacyl glycerol lipase
Oxidation: via cyclooxygenase and lipoxygenase pathway
what are the two amino acids apart of the EAA
Glutamate: derived from alpha ketoglutarate, and its metabolic and transmitter pool is strictly seperated
Aspartate: Often co-localized with glutamate,
serves as neurotransmitter on its own in visual cortex and pyramidal cells
Metabolic and transmitter pool strictly seperated
NMDA receptor
N-Methyl-D-Aspartate receptor
Ionotrophic
GLutamate and apsartate all activate them in the body
when activate allows for an influx of calcium
Has multiple modulatory sites
-glycine binding site
How does Glycine and Magnesium interact wiht the NMDA receptor
Glycine site: required co-agonist, but it alone cannot open the channel
Both EAA and glycine must be present for the channel to open
Magnesium site:
Found within the channel itself
blocks the channel at resting membrane potential
Prevents cacium influx when the channel opens
makes the NMDA receptor both ligand and voltage gate
How does PCP interact with the NMDA receptor
Horse tranquilizer
blocks the channel
How does the Non-NMDA receptor work and what are their names
AMPA
Kainate
ionotropic but allows a Na+ influx
Contains modulatory sites
-Benzodiazepines bind to a modulatory site and reduces the amount of sodium influx
Glutamate/Aspartate are the endongenous ligands
AMPA is the exogenous agent
What is the difference between the non-NMDA and NMDA epsp that they produce
Non-NMDA produce a typical exitatory post synaptic potential that is relative short onset and duration
While activation of the NMDA receptors produces a “long” latency epsp with a long duration
what are the functions of the non-NMDA and the NMDA receptors
Non-NMDA:
primary sensory afferents
upper motorneurons
NMDA:
critical in short and long term memory function
synaptic plasticity in many forms
EAA metabotropic receptors
Group 1: Gq
(mGlu1, mGlu5)
Group 2: Gi
(mGlu2 mGlu3)
Group 3: Gi
(mGlu4, mGlu6, mGlu7, mGlu8)
these exist in both pre and post synapses
presynaptic: control NT release
Post-synaptic: learning, memory, motor systems
What limits the action of EAA
glial cells: convert EAA back to glutamine
Nitric oxide
What are the neural functions of Nitric oxide
Memory:
- long term potentiation
- in hippocampus and cerebellum
Cardiovascular and respiratory control
-pons and medulla
Effects of NO and downside
used for free radicals to breakdown bacteria
also used for relaxation of the bloodvessels
however:
Very unstable
makes free radicals
high concentrations it is toxic to neurons
