CNS Neurotransmitters Flashcards
What are neurotransmitters? What do they produce?
chemical signals from presynaptic nerve terminals where they can bind to receptors on post-synaptic cells;
transient changes in electrical properties of target cell, leading to variety of effects
What are the 2 major types of neurotransmitters?
small molecules and neuropeptides
Give examples of small molecules neurotransmitters. Give describe of neuropeptides.
small molecules: ACh, amino acids (glutamate, GABA, glycine), biogenic amines (dopamine, NE, serotonin
neuropeptides: more than 100 types, 3-36 aa long
How is concentration of neurotransmitter regulated?
neurotransmitter synthesis, packaging, release, and removal
What does removal of neurotransmitter from the synaptic cleft do?
terminates transmission
How is the specificity of a neurotransmitter determined by its life cycle?
life cycle specific to each neurotransmitter
Compare and contrast synthesis and packaging of small molecules and neuropeptides
SM: made in presynaptic terminal, packaged in vesicle transporters; respond fast to increased demand (made in nerve terminal)
NP:made in cell body, packaged, transported along entire axon; cannot respond rapidly to inc demand
What are the 2 types of neurotransmistter receptors? Describe them.
Ionotropic; ligand-gated ion channels that open in direct response to ligand binding (4-5 subunits); each contanin 3 or 4 transmembrane domains
-multiple subunits can be assembled to generate a diverse set of receptors
metabotropic neurotransmitter receptors
-G protein coupled receptors that activate G-proteins in response to ligand binding
What allows the ligand to go through the ionotropic receptors?
Confirmational shift allows ions to go through
How many subunits are combined to make a functional ionotropic receptor?
4 to 5 subunits
How many transmembrane domains are typically associated with metabotropic receptor? How is their function different from ionotropic receptors?
7; second messenger system used
Both metabotropic and ionotropic receptors exist as many different types because
it increases diversity of their properties and functions
What is acetylcholine?
small molecule neurotransmitter that is important for attention, arousal, and reward plasticity
enhances sensory functions upon waking
damage to cholinergic system is associated with the memory deficits in AD
wherew is Ach found in the PNS? CNS?
PNS: neuromuscular junction
synapses in ganglia of visceral motor system
CNS: interneurons in the brainstem and forebrain
large motor neurons in the basal forebrain that project to cerebral cortex
(function unclear)
The precursor to ACh is
acetyl coA and choline
The receptors responding to ACh are
ionotropic and metabotropic receptors
ACh is removed by____. It’s mechanism is____.
acetylcholinesterase; cleaves ACh into acetate and choline
Sarin/organophosphates are dangerous to humans because
inhib acetylcholinesterase and cause continued muscular depolarization–>refractory to added ACh–>results in muscular paralysis
ACh is packaged in
synaptic vesicles by a ACh transporter
Ionotropic ACh receptors function as____. What do they mediate?
excitatory cation selective channels; mediate synaptic transmission at NMJ
Compare and contrast neuronal and muscular receptors.
They both have 5 subunits, but have different compositions
Metabotropic ACh receptors mediate most ACh effects in the _____.
brain
Where are muscarinic receptors highly expressed?
forebrain
What is the role of muscarinic recpetors in the periphery?
regulate autonomic effector organs (heart, smooth muscle, etc
Atropine and scopalomine are useful treatments because they
they are ACh antagonists
Myasthenia Gravis onset occurs in
young women and old men
What are some of the symptoms of myasthenia gravis?
muscle fatigue that worsens late in the day or after repeated exercise; improves with rest
diplopia and ptosis
difficulty speaking swallowing and chewing
weakness and fatigue in arms and legs
Myasthenia occurs due to
autoimmunity; antibodies against nAChR, increased turnover of the receptors
-altered structure of NMK because of decreased AChR–>sparse and shallow junctional folds and expanded synaptic cleft
The major treatments for Myasthenia Gravis are
cholinesterase inhbitors, thymectomy, corticosteroids, and immunosuppresants
The most prominent transmitter in the brain is
Glu
Glu is used by nearly all ____ neurons, which make up over____ of all brain synapses`
excitatory; 1/2
How can Glu contribute to negative consequences in the brain?
neuronal death during stroke bc O2 deprivation slows reuptake
hypoglycemia, trauma, and repeated intense seizures
Can Glu pass the blood brain barrier?
no, but the glutamine can
The precursor of Glu is
glutamine or transamination of alpha-ketoglutarate
Glu is packaged into
sunaptic vesicles by vesicular Glu transporter
Glu is removed from the synaptic cledt by
high affinity Glu transporters on both the nerve terminal and nearby glial cells
What is the role of glial cells in Glu life cycle
covert Glu back to glutamine and transported out of the cell and into nerve terminals
What are the 3 types of Glu ionotropic receptors?
NMDA, AMPA, and kainate
What is special about NMDA
Ca can pass thru, ion flow is voltage dependent and Gly is required to open the channel
There are ____ classes or metabotropic Glu receptors. When activated they ?
3; increase or decrease excitability of postsynaptic cells
GABA and Gly are the ?
GABA is used by
Gly is used by
major inhibitory neurotransmitters
local interneruons and Purkinje cells of the cerebellum
Gly predominantly used at synapses in spinal cord
GABA T is converted to ?
glutamate—>glutamine
GABA is transported by
synaptic vesicles
GABA is removed by
re-uptake into terminal and glia
Decreased GABA can cause
epilepsy
GABA is synthesized from
Glu using PLP from Vit. B6
Gly is synthesized from
Ser in the nerve terminal
Gly is packaged into
synaptic vesicels by the vesicular inhibitory transporter
Gly is removed by
re-uptake into terminal and glia
Gly in excess causes
neonatal diseases characterized by lethargy and mental retardation; transporters are deficient
What types of receptors are used by Glu and GABA
Ionotropic: GABAa and GABAc; Gly; inhibitory Cl channels
Metabotropic: GABAb
GABAb produces
inhibitory post synaptic response
GABA angonists include
benzodiazephines
Gly receptors are inhibited by ?
It is used as ?
strychine - rat poison because it causes overactivity in the spinal cord
Activation of ? produces inhibitory post synaptic responses
GABAb
GABA reuptake inhibitors can also be used to treat
anxiety and depression
Glu is made and utilized
relatively ubiquitously across the brain
Biogenic amines are synthesized, but there receptors are
in specific regions of brain, not ubiquitous; ubiquitous
Biogenic amines are critical for maintaining
mental health
80% of brain dopamine found in ?
Receives major input from ?
corpus striatum and substantia nigra
The function of neurons in the substantia nigra
coordination of body movements
What happens when there are decreased levels of dopamine? How is this treated?
neurons degenerate; with L DOPA in the striatum
The midbrain dopamine center projects from the
ventral tegmental area to ventral parts of the striatum
The midbrain dopamine system is involved in
motivation, reward, and reinforcement
When people are on cocaine dopamine levels increase by
their interference with the dopamine transporters
Dopamine plays a minor role in
the cortex; regulates emotional behavior (impulsivity)
NE containing neurons are found in
locus coeruleus and project to a variety of forebrain and brainstem targets
NE regulates
sleep and wakefulness, attention and feeding
In the PNS NE
is a major transmitter of sympathetic motor system
Catecholamine receptors are all
metabotropic
Dopamine receptors act by
activating or inhibiting adenylyl cyclase
Antagonists of dopamine receptors in the medulla used as
anti-emetics
NE receptors are
alpha and beta adrenergic receptors;
Agonists and antagonists of NE are used in
many conditions
Catecholamines are removed by
reuptake into terminal mediated by transmitter specific membrane transporters
cocaine causes an net increase in
dopamine production
amphetamines cause net increase in
NE and dopamine
Serotonin is found in
raphe nuclei in upper brainstem, project widely to the forebrain and brain stem
Serotonin functions to
regulate sleep, eating, arousal, and wakefulness
Drugs used to treat anxiety and depression act on
serotonergic neurons
Serotonin reuptake is mediated by
SERT
Metabotropic serotonin receptors are the
major receptors
Metabotropic serotonin receptors function to ?
When impaired they
when activated they
mediate emotions, circadian rhythms, motor behaviors and mental arousal
cause psychiatric disorders
mediate satiety and decreased food consumption
Ionotropic receptors (minority)
non selective excitatory channel; target for many drugs
anti-physchotic drugs
block dopamine receptors suggesting excess dopamine releasemay cause some psychotic illness like schizophrenia
anti-anxiety drugs
MAO inhibitors block breakdown of biogenic amines, inhibitors of serotonin receptors
anti-depressants (3 classes)
MAO inhibitors, tricyclic anti depressents, SSRIs
Peptide neurotransmitters modulate
emotion, perception of pain, stress response
Biological action of peptides determined by
amino acid sequence
What are the 5 categories of amino acid sequences
brain-gut peptides, opioids, pituitary, hypothalmic releasing, miscellaneous peptides
Neuropeptides are synthesized by
cleavage of ER targeting signal from pre-propeptide, processed into propeptides in ER by removal of ER targeting signal,
final processing to individual active peptides occurs in vesicels after they bud
peptide neurotransmitters are often coreleased with
small molecule neurotransmitters
peptides are removed from the synaptic cleft by
peptidases
endopeptidases
make more active peptides within the synaptic cleft by endopeptidases
peptides use
metabotrophic receptors
Opoid receptors are
widely distributed, can act as depressants, and morphine is an opioid that is one of the most effective analgesics
