NTS Flashcards
this hypothesis states that all axon terminals of a single neuron use one and only one NT though co release of multiple transmitters has been documented?
Dales Hypothesis
the first transmitters of the PNS to be discovered?
Ach and Norepi
what is the general approach of NT release? T/F can be manipulated pharmacologically
synthesis storage release presynaptic receptor high affinity reuptake postsynaptic receptor transmitter metabolism postsynaptic response
ACh is synthesized by what enzyme? via what substrates
choline acetyltransferase (ChAT)
AcCoA + Choline
where does the AcCoA come from? choline?
mitochondrial metabolism of pyruvate
diet and 50% of ACh production uses recycled choline following high affinity reuptake
what terminates cholinergic transmission by degrading ACh to choline and acetate? where are these localized
choline esterase like acetylcholine esterase and made in the liver.
ACh synapses
name the agent based on this effect:
ACh depletion
-Napthylvinyl pyridine
name the agent based on this effect:
release vesicles, depleting number for future use
+B-Bungarotoxin
+Black widow spider venom (BWSV)
name the agent based on this effect:
few vesicles released
-Botulinum toxin
name the agent based on this effect:
deplete ACh because choline is scarce
-Hemicholinium
name the agent based on this effect:
prolongs ACh transmission, over stimulation
2 agents that are reversible and irreversible
-reversibly
Neostigmine
physostigmine
(medically useful)
-irreversibly Malathion Nerve gas (deadly but also useful) myasthenia gravis
what are is the purpose of nicotinic and muscurinic receptors and their subtypes?
they are found in different tissues and this allows fro more specific drugs with fewer side affects
dopamine-DA, norepinephrine-NE, epinphrine-EPi
catecholamines
what are the stages for the synthesis of catecholamines?
L-tyrosine L-Dopa Dopamine Norepinephrine Epinephrine
what converts L-Tyrosine to L-Dopa?
tyrosine hydroxylase (cytosolic)
what converts L-Dopa to dopamine?
dopa decarboxylase (in many tissues)
what converts dopamine to norepinephrine?
dopamine-B-hydroxylase (inside many vesicles of cells that release NE)
what converts norepinephrine to epinephrine?
phenylethanolamine-N-methyl-transferase (PNMT) (cytosolic)
what it tyrosine hydroxylase inhibited by?
alpha methyl tyrosine
what is Dopa decarboxylase inhibited by?
alpha methyl dopa
what is dopamine-B-hydroxylase inhibited by?
diethyldithiocarbamate
what is phenylethanolamine-N-methyl-transferase stimulated by?
corticosteroids
where is epinephrine mainly found?
adrenal medulla and brainstem
what causes the release of NTs?
elevated intracellular Ca++
what agent depletes the transmitters?
alpha methyl tyrosine
alpha methyl dopa
diethyldithiocarbamate
what agent displaces NT from vesicles, causing initial release but long term depletion? for DA
amphetamines
alpha-OH-butyrate for DA
this is a stress hormone that enhances epi synthesis in the adrenal medulla?
cortisol
this increase NE in the cleft and leads to long term NE depletion?
cocaine
this enhances NE in the cleft?
desipramine and other tricyclic antidepressants
this is a toxic compound taken up and destroys the terminal? this is used to produced Parkinsonism in animals
6-OH-dopamine
this leads to long-lasting NE depletion in vesicles
reserpine
what enzymes are used to produce VMA(NE and EPI) and HVA (DA)? found in the urine
monoamine oxidase
catechol-o-methyl transferase
catechol-o-methyl transferase (COMT) inhibitor?
tropolone
what is the effect of MAO inhibitors?
it increases the DA, NE, EPI in nerve terminals and allows for more incorporation into vesicles so more NE enters the vesicles and more NE is released
what are MAOI’s used for?
antidepressants and blood pressure regulators
where are the cell bodies of the noradrenergic neurons found?
locus coeruleus of the 4th ventricle
where are the dopaminergic cell bodies found?
axons
tract
substantia nigra of the midbrain and most axons go to the corpus striatum (caudate and putamen) via the niagrostriatal tract
what causes degeneration of the niagrostriatal tract?
MPTP
what is MPTP an analog of what drug?
meperdine
some DA neurons projet to the forebrain, what drugs specifically target synapses by blocking transmission?
antipsychotic drugs like haloperidol or chlorpromazine
what is the other name for 5-hydroxytryptamine or 5-HT?
serotonin
where is serotonin synthesized from?
L-tryptophan
what ceases the serotonin transmission?
Na+ dependent high affinity reuptake by axon terminals and glia
what are the serotonin inhibitors? what is the effect
clomipramine
imipramine (prozac)
fluoxetine (Zoloft)
trazodone
tranylcypromise
act to enhance serotonergic transmission and have been used in treating depression, OCD and others
what is sertonin transmission involved in?
eating, sleep, sexual behavior, circadian rhythmicity, neuroendocrine function and affect
how many classes of serotonin receptors are there?
what are the effects
4 major classes 5 HTI-5 HT4
increase or decrease cAMP
increase or decrease K+ permeability
stimulate ligand gated ionophore
what is the primary excitatory NT of the CNS?
glutamate
what has glutamate been implicated in?
epilepsy, brain damage and learning
what terminates the glutamate transmission?
Na+ dependent high affinity reuptake by the neurons and glia
what are the 4 classes of glutamate receptors? which ones are ionotropic and metabotropic?
NMDA
AMPA
Kainate
ionotropic
ACPD (increase Ca2+)
AP4 (decrease cAMP, cGMP)
metabotropic
what are the inhibitory NTs?
GABA and glycine
this is the main inhibitory NT of the brain, GABA released by what?
lowered gabaergic transmission is implicated in?
GABA
interneurons
Huntington’s disease, epilepsy, tardive dyskinesia, alcoholism, schizophrenia, and sleep disorder
what is GABA synthesized from?
glutamate by glutamic acid decarboxylase
what are the GABA receptor types? name the agonists and antagonist?
GABA A and B
GABA A best characterized
+isoguvacine
-bicuculline
GABA B involved in presynaptic inhibition
+baclofen
-phaclofen
what do the GABA A receptors have binding sites for?
barbiturates and benediazepine
what stimulates the benediazepine site?
diazepam
what stimulates the barbiturate site?
phenobarnitol
pentobarbitol
Cl- channel
what stimulates and inhibits the GABA site?
muscimol (hallucinogenic mushroom) stimulates
bicuculline (a convulsant)
what enhances the Cl- conductance at the channel and depresses?
ETOH
Benzos and Barbs
what is the principal inhibitor of the spine?
glycine, this opens the Cl- channel to produce IPSP and is inactivated by reuptake causing skeletal muscle to not contract
what are the glycine agonist and antagonist?
agonist:
other amino acids not GABA
antagonist:
strychnine (muscles contract)
