Neurotransmitters and their Receptors Flashcards
Chemical signaling consists of a _____, a _____, and a _____.
neurotransmitter
receptor
ion channel
Acetylcholine is an _____ neurotransmitter.
excitatory
Glutamate is an _____ neurotransmitter.
excitatory
GABA is an _____ neurotransmitter.
inhibitory
Glycine is a _____ neurotransmitter.
inhibitory
Catecholamines (_____, _____, _____) are _____ neurotransmitters.
epinephrine
norepinephrine
dopamine
excitatory
Serotonin is an _____ neurotransmitter.
excitatory
Histamine is a _____ neurotransmitter.
excitatory
Ionotropic receptors are _____ channels.
ligand-gated
Metabotropic receptors are _____ receptors.
G-protein-coupled
Ionotropic Receptors (types)
- Glutamate receptors (NMDA,AMPA/Kainate)
- Nicotinic acetylcholine receptor (nAChR)
- 5-HT(sub3) receptor
- GABA(subA) receptor
- Glycine receptor
- Purinergic receptors
G-protein coupled receptors are _____ proteins consisting of ______ transmembrane
domains.
monomeric
7
Domains ,,_,and _ of GPCRs make up the
neurotansmitter binding region.
II, III, VI, and VII
G-proteins bind to both the loop between domains _ and _ and the _____.
V
VI
C-terminus (string from helix-7)
Biogenic Amines
DA EPI NE Histamine Serotonin
nAChR consists of _ subunits.
Muscles: _____
Neurons: _____
5
αα:β:γ:δ
ααα:ββ
In nAChR, the _____ bind acetylcholine.
α-subunits
Each subunit of the nAChR consists of _
transmembrane spanning _____.
4
α-helices
The _____ surround the channel of the nAChR.
M2 subunits
Binding of acetylcholine to the two alpha subunits
results in a _° rotation of all _____ helices.
15
M2
The cytoplasm side of the nAChR receptor has
rings of high _____ charge that determine the
_____ of the receptor and remove the
_____ of the passing ions.
negative
cation specificity
hydration shell
Binding of _ ACh molecules results in a _____ of the M2 helices
2
twisting
The nAChR is a _____
cation channel.
non-selective
Higher driving force for _____ typically results in an _____ current and an _____.
Na+
inward
EPSP
Precursors of acetylcholine
Acetyl coenzyme A
choline
The enzyme _____ catalyzes Acetylcholine.
choline acetyltransferase (ChAT)
_____ load ~_ ACh molecules into each vesicle.
Vesicular ACh transporters
10
After release into the synapse, _____ breaks up ACh into
_____ and _____.
acetylcholinesterase
acetate
choline
A _____ transporter
takes choline back up into the presynaptic terminal.
Na+/choline
Myasthenia gravis is treated with
reversible acetylcholine-esterase inhibitors (e.g. neostigmine)
Myasthenia Gravis is the result of ____ caused by ____.
an autoimmune response
circulating antibodies that block AChRs at the post-synaptic neuromuscular junction
ACh has difficulty binding due to _____ of the binding site.
IgG blockade
Irreversible Acetylcholinesterase inhibitors
completely inhibit ACh breakdown
Treatment of acetylcholinesterase inhibition involves combined administration of a _____ and the AChE antagonist _____.
muscarinic receptor antagonist (atropine)
pralidoxime
neurotoxins such as snake poisins, curare (plant) and conotoxins (cone snails) are _____.
nAChR antagonists
Chewing betel nuts releases _____, a nicotinic agonist.
arecoline
Enzyme _____ catalyzes glutamate from glutamine
glutaminase
VGLUT
vesicular glutamate transporter
EAAT
excitatory amino acid transporter
precursor of glutamate
glutamine
released by glial cells
glutamate receptors are _____.
non-selective cation channels
NMDA-R serves as a _____.
coincidence detector
NMDA-Rs require _____ as co-agonist.
glycine
NMDA current involvement in an action potential is maximized with ____.
no Mg2+ block
Ca2+ influx through NMDA-Rs results in
_____ and eventually _____ and ____.
AMPA-R phosphorylation (early phase)
gene transcription
protein synthesis
(late phase)
mGluRs have _____ and can be _____ or _____
slow responses
excitatory
inhibitory
mGluR group 1
(mGluRs 1 and 5)
excitatory, G(q) coupled
mGluR group 2
(mGluRs 2 and 3)
inhibitory, G(i/o) coupled
mGluR group 3
(mGluRs 4, 6, 7, and 8)
inhibitory, G(i/o) coupled
Group I mGluRs increase _____ and are mostly _____.
NMDA
postsynaptic
Group II mGluRs reduce _____, decrease _____ release, and decrease _____.
cAMP
transmitter
NMDA
Group II mGluRs are mostly _____ and on _____.
presynaptic
glia cells
Group III mGluRs reduce _____, decrease _____ release, and decrease _____.
cAMP
transmitter
NMDA
Group III mGluRs are mostly _____.
presynaptic
GAD
glutamate decarboxylase;
catalyzes glutamate to GABA
VIAAT
vesicular inhibitory amino acid transporter
GAT
GABA transporter (removal from synaptic cleft)
Ionotropic GABA receptors
GABA(A) and GABA(C)
The effects of GABA agonists (e.g. benzodiazepines [Valium] and barbiturates)
- anxiolytic (anxiety-reducing)
- anesthetic
- sedative-hypnotic
- anti-convulsive
Both _____ or _____ facilitate the ability of GABA to activate the receptor and opening of the chloride channel.
benzodiazepines
barbiturates (or alcohol)
Barbiturates increase the _____.
length of channel openings
Benzodiazepines increase the _____.
frequency of channel openings
Depolarizing synaptic potentials can inhibit neurons as long as the _____ is more hyperpolarized (negative) than the _____.
E(Cl-)
action potential threshold
In developing neurons the intracellular Cl- concentration is controlled by the _____, yielding high intracellular levels of _____.
Na+/K+/Cl- co-transporter
Cl-
In adult cells a _____ pumps Cl- out of the cell, lowering the _____, making ECl- much more negative (leads to hyperpolarization).
K+/Cl- co-transporter
internal Cl-
Shunting inhibition
If ECl- is equal to RMP, opening of Cl- channels does not hyperpolarize the cell, yet will act inhibitory on simultaneous EPSPs
Metabotropic GABA receptors
GABA(B)
mGABAR stimulate _____, leading to _____.
opening of K+ channels
hyperpolarization
mGABAR inhibit _____, leading to _____.
Ca2+ channels
hyperpolarization
mGABAR have _.
7 transmembrane domains
Activation of presynaptic GABA(B) autoreceptors can inhibit release of _____ from the terminal.
GABA
Presynaptic GABA(B) receptors inhibit release of ___, ___, and ___.
dopamine
norepinephrine
serotonin
catecholamines are released by the _____ in response to psychological stress or low blood sugar levels.
adrenal glands
Effects of catecholamines typically include
increases in heart rate
blood pressure
blood glucose levels
general reaction of the sympathetic nervous system
In the CNS, catecholamines act as _____, influencing the effects of other classical neurotransmitters.
neuromodulators
_____ catalyzes the reaction of L-Tyrosine to L-DOPA.
Tyrosine Hydroxylase
TH
_____ catalyzes the reaction of L-DOPA to DA.
Aromatic L-amino acid decarboxylase
AADC
_____ catalyzes the reaction of DA to NE.
Dopamine B-Hydroxylase
DBH
_____ catalyzes the reaction of NE to EP.
Phenylethanolamine N-Methyltransferase
PNMT
Catecholamines do not evoke EPSP or IPSP by themselves, rather make EPSP / IPSP _____.
larger or smaller
Catecholamines alter ion channels to modulate _____, so that when synaptic inputs arrive the neuron is either _____ or _____.
cell’s excitability
more ready to fire action potentials
hyperpolarized / less excitable
The catecholamine _____ is the reate-limiting enzyme in the synthesis of all catecholamines.
tyrosine hydroxylase
Tyrosine hydroxylase is upregulated by _____, _____, _____, and _____.
stress
caffeine
nicotine
morphine
Tyrosine hydroxylase is downregualted by _____.
antidepressants
Symptoms of parkinson’s disease
tremors muscle rigidity akinesia bradykinesia postural instability
Treatment of parkinson’s disease involves the replacement of lost DA with _____ or _____.
L-DOPA
DA
GABAergic neurons in the _____ are the origin of projections that control (disinhibit) the thalamus, which in turn controls areas in the cortex that _____.
striatum
initiate movement
Parkinson’s Disease
Loss of DA inhibition of GABAergic projection neurons.
Addictive drugs target the _____, which includes the dopaminergic projections from the ventral tegmental area (VTA) to the _____ and other forebrain structures.
brain reward circuit
nucleus accumbens
Dependence
an adaptive state that develops in response to repeated drug administration
Cessation of drug use can lead to ____.
withdrawal symptoms
Tolerance
refers to the diminished effect of a drug after repeated administration at the same dose, or the need to increase the dose to produce the same effect.
sensitization
repeated drug administration leads to stronger effects at the same dose.
Drugs of abuse typically release - times the amount of dopamine that natural rewards do.
2
10
VMAT
vesicular monoamine transporter
DAT
Dopamine transporter
COMT
catechol O-methyltransferase
enzyme that degrades all catecholamines
MAO
monoamine oxidase, enzyme that degrades all monoamines
HVA
homovanillic acid
Cocaine and amphetamines inhibit _____.
the re-uptake of dopamine
Cocaine blocks _____ which increases the lifetime of dopamine in the synaptic cleft.
the dopamine transporter (DAT) (blocks dopamine re-uptake)
Amphetamines increase _____ and block _____.
dopamine release
re-uptake
Amphetamines enter the presynaptic terminal (via DAT, or through direct diffusion) and release _____ from the vesicles by making the dopamine transporters _____.
dopamine
work in reverse
NE forms at the _____.
locus coeruleus
EP forms at _____.
meduallary epinephrine neurons
_____ catalyzes the reaction of DA to NE.
Dopamine B-Hydroxylase
NET
NorEpinephrine Transporter
NE and EP are degraded by ____.
MAO
MAO
enzyme that degrades all monoamines
NE and EP act _____ on 2 types of GPCRs: ____ and ____.
postsynaptically
A-
B-Adrenergic Receptors
_____ inhibits VMAT and depletes NE stores.
Reserpine
_____ inhibits COMT.
Tropolone
_____ inhibits tyrosine hydroxylase and NE synthesis.
AMPT
_____ is a norepinephrine and dopamine reuptake inhibitor.
Methylphenidate (Ritalin)
Clonidine is an _____.
α2 adrenergic agonist
α2-receptors are _____ (inhibits NE release).
autoreceptors (presynaptically)
5 groups of Neuropeptides:
- brain / gut peptides
- Opioid peptides
- Pituitary peptides
- Hypothalamic releasing hormones
- “other peptides”
Pre-propeptides are present on the _____.
rough ER
Propeptides are present on the _____.
trans-Golgi network
Can different peptides can be released from the same vesicle?
yes
Morphine, heroin, and synthetic opiates such as methadone and fentanyl are potent _____.
analgesics
3 groups of endogenous opioid receptor ligands:
- Endorphins (ENDOgenous moRPHINE)
- Enkephalins
- Dynorphins
Enkephalins, endorphins and dynorphins are released in the _____.
periaqueductal gray
Enkephalins are also released directly in the spinal cord to blunt the effects of _____.
nociceptor (C-FIBER) activation
The _____ have a high affinity for enkephalins and beta-endorphin, but low affinity for dynorphins.
μ opioid receptors
Morphine (heroin) and codeine bind to _____.
μ opioid receptors
Main locus of action of heroin and codeine is in the _____.
VTA
______ is the main active component of marijuana.
tetrahydrocannabinol (THC)
Endocannabinoids:
2-AG
anandamide
2 types of cannabinoid receptors (G-protein coupled receptors):
- CB1 mainly expressed in the CNS and
* CB2 mainly expressed in immune cells
low doses of cannabinoids tend to reduce _____, whereas high doses _____ theses behaviors.
anxiety-like behaviors
increase
Anxiolytic effects:
- Euphoric feelings of happiness, talkativeness, dream-like state.
- Feelings of dizziness or fuzziness.
- Contagious laughing or joking
- Increases appetite “munchies”
THC has _____ as seen in studies with drug discrimination, brain stimulation reward, and intravenous self-administration.
acute reinforcing effects
THC increases the release of dopamine in the shell of the _____.
nucleus accumbens
Physiological effects of (Endo-) cannabinoids
Various effects, including
• inhibition of adenylate cyclase,
• modulation of voltage-dependent calcium, and
• potassium channels
Enhancement of endocannabinoid signaling produces _____.
anxiolytic and antidepressant-like effects
endocannabinoid system is involved in the regulation of ____.
emotional states
Endocannabinoids act as a retrograde messenger to regulate ____.
GABA release
Nitric oxide (NO)
gaseous (retrograde) messenger
Nitric oxide, is synthesized from _____ by various nitric oxide synthase (NOS) enzymes.
arginine and oxygen
NO readily passes through ___.
membranes
NO stimulates synthesis of _____.
second messenger that activates a protein kinase
cGMP (via guanyl cyclase)
