neurotransmitter systems Flashcards
what was the first neurotransmitter?
acetylcholine (loewi)
cells that produce and release ACh are…?
cholinergic (dale)
cells that produce and release norepinephrine are…?
noradrenergic (dale
cells that produce and release GABA are…?
GABAergic
cells that produce and release glutamate are…?
glutamatergic
cells that produce and release peptides are…?
peptidergic
what are the classifications of a NT?
- must be synthesized and stored in presynaptic neuron
- must be released by presynaptic terminal in response to stimulation
- MUST BE CA2+ DEPENDENT
- when applied experimentally, molecule must produce a response in the postsynaptic cell as occurs
immunocytochemistry
make antibodies to specific transmitters or enzymes which synthesize the transmitter
in situ hybridization
detect RNA expression using a specific probe, labeled with radioactivity to colored or fluorescent product
how do you study NT release?
- test fluid near axons or cells for substance after stimulation and chemically analyze
- use in vitro slice, HIGH K+ and Ca2+ dependency to characterize
what can be used to control signaling in individual neurons?
optogenetics
can two different NTs bind to the same receptor?
NO
T or F: each neuron can bind to different subtypes
TRUE
neuropharmacology
use agonists and antagonists to classify receptor subtypes
cholinergic receptors - nicotinic
agonists = nicotine antagonists = curare
cholinergic receptors - muscarinic
agonists = muscarine antagonists = atropine
glutamatergic receptors (3 types)
agonists = AMPA, NMDA, kainate
ligand-binding receptors
use labeled ligands to bind specifically to receptors
- can be NT, agonist, or antagonist
- can be toxins or components of venom
molecular analysis of NT receptors are used for…?
- cloning of many receptor cDNAs
- protein sequencing
- diversity of subtypes larger than expected from binding and pharmacology
most NTs are….
amino acids, amines made from amino acids, or peptides
dale’s principle
neuron has only ONE neurotransmitter, peptide containing neurons violate this idea
ACh (acetylcholine)
neurotransmitter at neuromuscular junction, made by ALL motor neurons in spinal cord and brain
basal forebrain neurons are used in
learning, memory and alzheimers
dorsolateral tegmenjtum of pons involved in…
forebrain activity in sleep, wakefulness, and in many circuits in ANS
choline acetyltransferase (ChAT)
required for synthesis, good marker for cholinergic cells
what is the rate-limiting step in cholinergic neurons?
the UPTAKE of choline
ACh is degraded by..? where?
acetylcholinesterase (AChE) i the synaptic cleft
___ and ___ dependent transporter proteins on synaptic membrane
Na+ and Cl-
uptake of ACh is regulated by…?
protein kinase C
increasing choline levels are used in diseases such as..
alzheimers
filling of vesicles is driven by..? which is powered by…?
H+ gradient powered by H+-ATPas (2 H+/ACh)
although unsure it is thought that changes in filling are controlled by?
changes in driving force OR number of transporters per vesicle
___ affinity for ACh
mM
catecholaminergic neurons are involved in…
mood, attention, and autonomic functions
properties of catecholaminergic neurons
- ALL contain tryosine hydroxylase
- are rate limiting
- end-product inhibition
- increased Ca2+ increases TH activity
what is present in large amounts in dopaminergic neurons?
dopa-decarboxylase
the amount of dopamine made depends on..?
the amount of dopa available
are catecholaminerfic neurons degraded in the synaptic cleft?
NO
how are catecholaminergic neurons transported back to the terminal?
by Na+ dependent transporters
what blocks transportation of catecholaminergic neurons back to terminal?
amphetamines and cocaine
when can catecholaminerrgic neurons be reloaded into the vesicle?
- after uptake
- degraded by monoamine oxidase (MAO) in mitochondira
dopamine-beta-hydroxylase
present in noradrenergic neurons and synaptic vesicles, but NOT in cytosol
adrenergic neurons contains..? synthesizes?
PNMT, synthesizes epinephrine (adrenaline)
where is PNMT found?
cytosol
where is NE made?
vesicle
where is NE released?
into cytosol
norepinephrine
major group of neurons in locus coeruleus, which project to numerous structures (cortex, hypothalamus, and hippocampus)
noradrenergic neurons modulate…
attention, feeding behavior, and sleep
what 3 NTs are removed from synapse and destroyed?
epinephrine, dopamine, and norepinephrine
major group of adrenergic cells are in the….
medulla
what is used to identify catecholaminergic neurons in pathways?
antibodies to enzymes
what medication is used to block reuptake of serotonin?
prozac, helps relieve depression
serotonergic neurons are important in regulation of…
sleep, mood, emotional behavior, and aggression
what regulates pain signaling in serotonergic neurons?
raphe nucleus neurons
how is synthesis regulated in serotonergic neurons?
amount of tryptophan in extracellular fluid
where is the precursor for melatonin located?
in the pineal gland
what type of medications are used to treat depression?
SSRI’s (flupxetine, prozac)
effects of ecstasy on serotonin
induces its release to produce sensory enhancement and empathy
which NTs are at the CNS synapses?
glutamate, GABA, and glycine
which is more concentrated by 2-3 times in other neurons or cells?
glutamate
which two amino acid neurotransmitters are in ALL cells?
glutamate and glycine
what is GABA synthesized from?
glutamate by L-glutamic acid-1-decarboxylase
T or F: GAD is present in glutamatergic neurons or glia
FALSE
T or F: GABA is only made in neurons that use it
TRUE
GABAergic neurons are a major inhibitory system in…
the nervous system
where are amino acid transmitters taken up?
by the nerve terminal by specific transporters
glutamate is involved in..
learning, memory, and motor functions
most excitatory neurons in the brain are…
glutamatergic
glutamate synthesis
does NOT cross BBB; made from glutamine or glucose and alpha-ketoglutarate
how is glutamate packed into vesicles?
VGLUT (3 known)
how is glutamate removed from cleft?
nerve terminals or astrocytes by Na-dependent EAAT
EAAT 3 and 4
neuronal transporters
EAAT 1 and 2
glia
neuronal membrane transporter
cotransport 10,000 times higher than in cleft
vesicular transporter
countertransport, may concentrate up to 100,000 times
most inhibition in the CNS?
GABA
what are GABA A and glycine receptors?
Cl channels, similar to nAChR
glutamate is a major ____ NT
excitatory
GABA is a major ____ NT
inhibitory
GABA signaling deficits associated with…?
- huntington’s
- parkinson’s
- schizophrenia
- senile dementia
what are modulators of GABA receptors? (also used to treat epilepsy)
barbitutrates
how is GABA packed into synaptic vesicles?
vesicular inhibitory amino acid transporter (VIAAT)
how is GABA removed?
high-affinity transporters (GATs) into neuron and glia
where is GABA broken down?
mitochondria
what is required as a cofactor for synthesis?
B6
GABA A and C
ionotropic
GABA B
metabotropic
ionotropic channels gate ____ and are ____
Cl- and are inhibitory
how is glycine synthesized?
from serine by serine hydroxymethyltransferase
how is glycine loaded into vesicles?
vesicular inhibitory amino acid transporter (VIAAT)
how is glycine removed from cleft?
plasma membrane glycine transporters
what is the antagonist in glycine receptors?
strychnine
what opens cation channel? (nucleotide receptor)
ATP
endocannabinoids
retrograde signaling, NOT in vesicles, membrane permeable, bind to CB1 receptors, inhibits presynaptic Ca2+ channel
ATP
excitatory NT in sensory and autonomic ganglia and in motor neurons
peptide NT
processed like proteins
- endorphins
- enkephalins
- dynorphin
- substance p
where do peptide NTs act through?
G protein-coupled receptors
nitric acid (NO)
- synthesized from arginine
- released by some postsynaptic neurons
- retrograde signal
- permeable
transmitter-gated channels
- five subunits
- each subunit type has a unique sequence, but are similar
- each subunit has 4 hydrophobic alpha-helical membrane spanning regions
- four types (alpha, beta, gamma, sigma)
ACh binding sites require ___ subunit
alpha
amino acid-gated channels
- mediate fast synaptic transmission in CNS
- involved in many systems and diseases
- selectivity
- conductance
- pharmacology
what are the 3 glutamate receptors?
AMPA, NMDA, and kainate
AMPA
permeable to Na+ and K+, NOT Ca2+. activation causes Na+ entry and depolarization, coexists with NMDA receptors
NMDA
permeable to Ca2+, inward current is voltage-dependent. Ca2+ entry important to many actions
GABA receptors are modulated by…
benzodiazapines (valium) to increase frequency of opening and barbiturates (phenobarbitaol) to increase channel open time
what are the common themes of ligand-gated ion channels?
- multiple subtypes
- each subtype with distinct pharmacology and electrophysiological properties
- 4 transmembrane regions
- binding sites at subunit interface
- multiple subunits-pentamer
G-protein coupled receptors
- extracellular loops from binding site for the ligands
- G-protein bind to some of the intracellular loops and are activated upon transmitter binding
- 100 G-protein like receptors known
G-proteins
- guanosine triphosphate (GTP) binding
- 20 kinds
- 3 subunits (alpha, beta, gamma)
shortcut pathway
binds to ion channels, 30-100 msec time scale, localized
second messenger cascades
multiple steps, activation of enzymes
signal cascades
- slow
- amplification
- many control points
- longer range signaling
- long lasting effects
