CNS Neurotransmitters Flashcards
1
Q
small molecule nts
A
aa-glutamate, aspartate, GABA, glycine
- ach
- biogenic amines-catecholamines-epi, norepi, dopamine
- serotonin
- histamine
- chemical signals released from pre-synaptic nerve terminals into the synaptic cleft where they can then bind to receptors on postsynaptic cells resulting in a transient change in the electrical properties of the target cell
- act over tiny distance
2
Q
peptide nts
A
- more than 100 different peptides
- 2-36 aa long
3
Q
nt life cycle
A
-concentration of nt in cleft controlled via regulation of: nt synthesis packaging release removal -removal terminates transmission -specific for each nt
4
Q
synthesizing and packaging
A
- small molecule:
- synthesized within pre synaptic terminal and packaged into vesicles by specific transport proteins in the vesicle membrane
- can respond to increased demand rapidly
- slow axonal transport but fast action
- neuropeptides:
- synthesized and packaged into transport vesicles within the cell body, then vesicles down fast
- cannot respond quickly to increased demand because systhesized in cell body
- release carefully regulated
5
Q
ionotropic receptors
A
- ligand gated ion channels that open in direct response to ligand binding
- consist of 4 or 5 subunits that each contain 3 or 4 transmembrane domains- have pore loop
- usually multiple subunits that can be assembled to generate a diverse set of receptors
6
Q
metabotropic receptors
A
-G protein coupled
activated G proteins modulate ion channels directly or indirectly through intracellular enzymes and second messengers
-monomeric proteins containing 7 transmembrane domains
-wide variety for most nts
7
Q
ionotropic receptor subunits
A
- wide variety
- ampa and nmda are ionotropic
- 4 or 5 combined to make a functional receptor
- there are a number of rules that govern which set of subunits are found within each receptors
- for most each has distinct properties
- same with metabotropic
8
Q
amino acid nt
A
- glutamate
- GABA
9
Q
biogenic amines
A
-dopa, norepi, serotonin
10
Q
Ach
A
- NMJ, synapses in ganglia of visceral motor system
- in CNS-interneruons in brainstem and forebrain
- large neurons in the basal forebrain that project to cerebral cortex
- function in CNS not as well understood-attention, arousal, reward plasticity, enhances sensory functions, damaged associated with memory deficits in AD
11
Q
Ach in cholinergic nerve terminals
A
- synthesized in nerve terminal from acetyl coA and choline
- packaged by vesicular Ach transporter
- removed from synaptic cleft via cleavage to acetate and choline by AchE
- choline taken up by nerve terminal via transporter and is used to make more Ach
- organophosphates and nerve gas can be lethal because they inhibit AchE causing accumulation
- continued depolarization, muscle paralysis
12
Q
Ach receptors 1
A
- nicotinic/ionotropic
- excitatory cation-selective channels
- mediate synaptic transmission at NMJ
- also present in CNS
- muscle and neuronal receptors have different subunit compositions, both consist of 5 subunits
13
Q
Ach receptors 2
A
- metabotropic/muscarinic
- mediate most Ach in brain
- highly expressed in forebrain
- also present in peripheral ganglia where they mediate responses of autonomic effector organs
- antagonists atropine (pupil dilation) and scopolamine (motion sickness) are therapeutically useful
14
Q
Myasthenia Gravis
A
- 14/100,000
- tired
- Achreceptor AI disease
- size of MEPPs reduced, EPPs reduced, probability of post synaptic AP reduced
- cholinesterase inhibitors, thymectomy, corticosteroids, immunosuppressents
15
Q
glutamate
A
- most prominent transmitter for normal brain function
- nearly all excitatory neurons in brain use it
- more than half of all brain synapses
- excitotoxicity
- high EC concentration toxic
- excessive activation can excite neuron to death
- thought to cause neuronal damage during strokes, oxygen deprivation slows glutamate reuptake
- considerable interest in using glutamate receptor antagonists to block excitotoxic nerve damage following stroke
- also involved in other acute forms of neuronal insult such as hypoglycemia, trauma, and repeated intense seizures
16
Q
glutamate in glutamatergic nerve terminals
A
- glutamate can’t cross blood-brain barrier but glutamine can
- synthesized in nerve terminal from glutamine
- can also be synthesized by transamination of alpha-ketoglutarate
- packaged into vesicles by vesicular glutamate transporter
- removed from synaptic cleft by high affinity glutamate transporters on both nerve terminal and nearby glial cells
- in glial cells, glutamate is converted into glutamine and then transported out of the cell and back into nerve terminals
17
Q
ionotropic glutamate receptors
A
- ionotropic-NMDA, AMPA, kainate
- excitatory cation selective Na channels
18
Q
NMDA
A
- Ca can pass through
- ion flow is voltage dependent because of Mg 2+ binding
- glycine binding is required to open channel
19
Q
metabotropic glutamate receptors
A
- three classes
- activation can increase or decrease excitability of post-synaptic cell
20
Q
GABA and glycine
A
- major inhibitory nt in CNS
- GABA is widely distributed in the brain, 1/3 of synapses
- used by local interneurons in purkinje cells of the cerebellum
- glycine is predominantly used at synapses in spinal cord
21
Q
GABA in GABAergic nerve terminals
A
- GABA synthesized in nerve terminals from glutamate, reaction requires pyridoxal phosphate derived from vitamin b6
- packaged into synaptic vesicles by the vesicular inhibitory amino acid transporter
- removed from synaptic cleft by specific transporters on nerve ternimals and nearby glia
- decreased GABA function can cause epilepsy
- GABA-T turns it into glutamate then glutamine and it becomes like glutamate cycle
22
Q
glycine in glycinergic nerve terminals
A
- synthesized in nerve terminals from serine
- packaged by vesicular inhibitory amino acid transporter
- removed from synaptic cleft by specific transporters on nerve terminals and nearby glia
- excess glycine caused by defects on glycine transporter causes neonatal disease characterized by lethargy and mental retardation
23
Q
ionotropic GABA and glycine receptors
A
- GABAa and GABAc
- inhibitory chloride channels
- GABA receptor agonists enhance GABAergic transmission
- benzodazepines-valium
- barbituates- anesthetics
- glycine receptor antagonist-strychnine-blocks receptors
- causes overactivity in spinal cord and brainstem leading to seizures-rat poison
24
Q
metabotropic GABA receptors
A
- GABAb
- widely distributed in brain
- activation produces inhibitory postsynaptic response
25
Q
dopamine, norepi, serotonin
A
- limited expression of genes for synthesis
- receptors more broadly expressed
- compared to GABA and glutamate all over
26
Q
biogenic amines
A
- aminergic neurons project widely in brain and help modulate intensity of more specific neuronal signals
- used by relatively few neurons in brain, but very important
- implicated in wide range of behaviors
- defects in functions implicated in most psychiatric disorders
- synthesis in nerve terminals
- packaged by vesicular monoamine transporter
- removed by reuptake into nerve terminals
- receptors are metabotropic, serotonin also has ionotropic
27
Q
catecholamine synthesis
A
- tyrosine converted to DOPA
- DOPA converted to dopamine
- dopamine to norepi
- norepi to epi
28
Q
sertonin synthesis
A
- tryptophan converted to 5-hydroxytryptophan
- 5-hydroxytryptophan converted to serotonin
29
Q
distribution of dopamine containing neurons and their projections- substantia nigra
A
- sends projections to striatum
- coordination of body movements
- parkinson’s
- treated with L-DOPA
- 80% of brain dopamine found in corpus striatum, which receives major input from substantia nigra
30
Q
midbrain dopamine system
A
- project from ventral tegmental area to ventral parts of striatium
- involved in motivation, reward, and reinforcement
- addictive drugs raise dopamine levels by interfering with reuptake by dopamine transporters
- minor projections to the cortex involved in emotional behavior
31
Q
projections from locus coeruleus-norepi
A
- to variety of forebrain and brainstem targets
- influences sleep and wakefulness, attention, feeding behavior
- PNS-prominent in sympathetic ganglion cells
- major transmitter of sympathetic motor system
32
Q
dopamine receptors
A
- act by activating or inhibiting adenylyl cyclase
- antagonists of receptors in medulla used as anti-emetics to treat nausea and vomiting
33
Q
norepi receptors
A
- a and b adrenergic receptors
- agonists and antagonists used therapeutically for many conditions
- cardiac arrhythmias and migraine headaches
- most of these effects are mediated by receptors in smooth muscle, not brain
34
Q
catecholamine removal from synaptic cleft
A
- reuptake into nerve terminals and glia
- mediated by transmitter-specific plasma membrane transporters
- cocaine inhibits dopamine transporter causing net increase in release of dopamine
- amphetamin inhibits both dopamine and norepi transporters causing net increase in release of transmitters
35
Q
serotonin-raphe nuclei in upper brain stem
A
- project widely to forebrain and brainstem
- implicated in regulation of sleep, eating, arousal, wakefulness, mood altering
- drugs used to treat depression-SSRI
36
Q
serotonin
A
- reuptake into nerve terminal by specific serotonin transporter
- metabotropic receptors
- implicated in emotions, circadian rhythms, motor behaviors, mental arousal
- impairment implicated in many psychiatric disorders
- activation mediates satiety and decreased food consumption
- ionotropic receptors-non-selective excitatory cation channel, targets of many drugs including some used to prevent nausea
37
Q
anti-psychotic drugs
A
-block dopamine receptors suggesting excess dopamine release may cause some psychotic illnesses such as schizophrenia
38
Q
anti-anxiety drugs
A
- MAO inhibitors block breakdown of biogenic amines
- inhibitors of serotonin receptors
39
Q
anti-depressents
A
- MAO inhibitors block breakdown of biogenic amines
- tricyclic anti-depressants block reuptake of NE and 5-HT
- SSRI act specifically on serotonin transporters
40
Q
peptide neurotransmitters
A
- implicated in modulating emotions, perception of pain, responses to stress
- biological activity is dependent on the aa seq
- 5 categories:
- brain gut
- opioid
- pituitary
- hypothalamic-releasing
- miscellaneous
41
Q
synthesis and processing of neuropeptides
A
- synthesized as pre-propeptides in in the ER in neuronal cell body
- processed into propeptides in ER by removal of ER targeting signal
- final processing to individual active peptides occurs in vesicles after they bud from trans Golgi
- individual pro-peptides can give rise to multiple active peptides within a single vesicle
42
Q
peptide neurotransmitters 2
A
- often co-released with small molecule
- removed from synaptic cleft via degradation by peptidases
- some peptides are degraded to more active peptides within the synaptic cleft by endopeptidases
- use metabotropic receptors-activated at low peptide concentrations and little is known
43
Q
opioid peptides
A
- widely distributed throughout brain
- tend to be depressants and can act as analgesics
- morphine binds to same receptors at opioid peptides
