lecture 7 part 2 Flashcards
what does NPY stand for
neuropeptide Y
what is the primary function of neuropeptide Y (NPY)
causes long lasting vasoconstriction
what does NO stand for
nitric oxide
true or false
NO is not a neurotransmitter
false - it is
what does CCK stand for
cholecystokinin (neurotransmitter)
what is the role of cholecysokinin (CCK)
may act as a co-neurotransmitter in some excitatory neuromuscular ENS neurond
enkephalin is related to what?
opioid peptides
explain what enkephalin and opioid related peptides do
inhibit acetylcholine release and inhibit peristalsis.
may stimulate secretion
galanin may play a role in what?
appetite-satiety mechanisms
what does GABA stand for
gamma-amino butyric acid
explain what GABA does
has relaxant effects on the gut
probably not a major neurotransmitter in the ENS
what does GRP stand for
gastrin releasing peptide
explain what GRP (gastrin releasing peptide) does
an extremely potent excitatory neurotransmitter to GASTRIC CELLS (stomach)
true or false
the metabolic rate increasing is part of a sympathetic response
true
a sympathetic response will cause _______ digestive and urinary functions
decreased
true or false
a sympathetic response will cause an increase in blood pressure
true
true or false
a sympathetic response will cause a deactivation of energy reserves
FALSE - activation
this is why most ppl lose weight when stressed
true or false
sweat glands are activated in the sympathetic response
true
parasympathetic division causes _____ metabolic rate
decreased
true or false
the parasympathetic division causes the activation of sweat glands
false - activation of all other glands like salivary and digestive
most autonomic nervous system regulations use what kind of feedback?
how does this relate to drugs
NEGATIVE FEEDBACK
negative feedback is important in the responses of the ANS to autonomic drugs
name the autonomic receptors
cholinergic and adrenergic
further classify the autonomic receptors
cholinergic - nicotinic and muscarinic
adrenergic – alpha adrenergic (alpha1 and alpha2) and beta adrenergic (beta 1,2,3)
what is the result of ligand binding to M1
formation of IP3 and DAG and increased intracellular calcium (works thru Gq!)
what is the result of ligand binding to M2
the opening of potassium channels and inhibition of adenylyl cyclase
(decreased heart rate)
what is the result of ligand binding to M3
like M1 - formation of IP3 and DAG and increased intracellular calcium
what is the result of ligand binding to M4
like M2 - opening of potassium channels and inhibition of adenylyl cyclase
(decreased heart rate)
what is the result of ligand binding to M5
like M1 - formation of IP3 and DAG and increased intracellular calcium
what are the typical locations of M1
CNS neurons
sympathetic postganglionic neurons
some presynaptic sites
what are the typical locations of M2
myocardium and smooth muscle
what are the primary locations of M3
exocrine glands
what are the primary locations of M4
CNS neurons
what are the primary locations of M5
vascular endothelium
name the 2 nicotinic receptors
NN and NM
what are the results of ligand binding to NN? what about ligand binding to NM?
both result in the opening of Na+ and K+ channels and DEPOLARIZATION
further classify the adrenoceptors
alpha 1 and alpha 2
beta 1,2,3
explain the result of ligand binding for beta1, beta2, and beta3 receptors
beta1 - contraction. stimulation of adenylyl cyclase and increased cAMP. found in heart and blood vessels
beta2 - relaxation. stimulation of adenylyl cyclase and increased cAMP. stimulates cardiac G under some conditions. found in smooth and cardiac muscle
beta3 - stimulation of adenylyl cyclase and increased cAMP. breaks down fats
explain what alpha 1 and alpha 2 receptors do
alpha 1 contracts through formation of IP3 and increased intracellular calcium
alpha 2 relaxes through inhibiting adenylyl cyclase and decreases cAMP
explain the typical locations of alpha 1 and alpha 2 receptors
alpha 1 - at postsynaptic effector cells especially smooth muscle
alpha 2 is at presynaptic adrenergic nerve terminals, platelets, lipocytes, and smooth muscle
for someone with hypertension, what kind of beta blocker is needed?
a SELECTIVE beta1 blocker.
if it is effective on beta1 and beta2, the person wouldnt be able to breathe
in general, what is the typical location of the dopamine receptors?
the brain
name all of the dopamine receptors and the result of ligand binding
D1, D2, D3, D4
D1 - stimulation of adenylyl cyclase and increased cAMP
D2 - inhibition of adenylyl cyclase and increased potassium conductance
D3, D4 - inhibition of adenylyl cyclase
name the 4 steps of acetylcholine transmission
synthesis
storage
release
action and termination
what is the name of the enzyme that breaks down acetylcholine?
what is it broken into?
acetylcholine esterase breaks down acetylcholine into choline and acetate
choline can be recycled and acetate is released out
explain how acetylcholine is synthesized and released
sodium and choline pass through the choline transporter on the membrane.
acCoA is from the mitochondria (from inside of the cell)
AcCoA and choline are joined toghether by ChAT (choline acetyltransferase)
newly formed acetylcholine is then transported into a vesicle through VAT (vesicular acetylcholine transporter)
acetylcholine is released from the vesicle when calcium enters the cytoplasm and through VAMPS (vesicle associated membrane proteins) exocytised with ATP and P
what blocks the synthesis of acetylcholine and how?
what drugs mimic this?
hemicholiniums
will not allow the transport of choline across the membrane.
antipsychotic meds mimic this
once acetylcholine has been synthesized, what happens
the acetycholine (now in the cytoplasm) needs to be stored in a vesicle
this is done through VAT (vesicular acetylcholine transporter)
what blocks acetylcholine from going into the vesicle
vesamicol.
blocks VAT and thus no vesicle
once acetylcholine is in the vesicle, what happens?
exocytosis out of the cell, and acetylcholine binds on its cholinergic receptor,
exocytosis occurs via VAMPs (vesicle associated membrane proteins) and the influx of calcium
what blocks the exocytosis of acetylcholine?
botulinum toxin
where is acetylCoA synthesized
in the mitochondria
where are mitochondria present in large numbers?
in the nerve ending
true or false
acetylcholine is synthesized in the cytoplasm
true
what enzyme synthesizes acetylcholine
choline acetyltransferase (ChAT)
what is VAT driven by?
what does VAT do?
VAT (vesicle associated transporter) transports the newly synthesized acetylcholine from the cytoplasm and into a vesicle.
it is driven by the efflux of protons
VAT can be blocked by…
vesamicol
most of the vesicular acetylcholine is bound to what?
VPG – negatively charged vesicular proteoglycan
where are vesicles concentrated and by what?
on the inner surface of the nerve terminal by SNARE proteins on the vesicle and on the inside of the terminal cell membrane
the release of acetylcholine from the vesicle is dependent on what
extracellular calcium
occurs when an action potential reaches the terminal and triggers sufficient influx of calcium ions
what inhibits the reuptake of norepinephrine
cocaine and tricyclic antidepressants.
NE will thus stay in the synaptic cleft longer
what happens when acetylcholine is released via exocytosis
binds on cholinoceptors (nicotinic + muscarinic)
when broken down, choline can be recycled and be transported back into the neuron through CHT, and acetate is released out
true or false
Acetyl-CoA is synthesized in the cytoplasm
FALSE - in the mitochondria
acetylcholine is synthesized in the cytoplasm
explain how acetycholine is stored in vesicles
vesicular ACh is bound to - charged VPG (vesicular proteoglycan)
these vesicles are on the inner surface of the nerve terminal by SNARE proteins that are on the vesicle (v-SNARES - synaptobrevin) and on the inside of the terminal cell membrane (t-SNARES - syntaxin and SNAP 25)
the release of acetylcholine from the vesicle is dependent on…….
extracellular calcium. occurs when an action potential triggers the influx of calcium via N-type Ca channels
calcium interacts with VAMP synaptotagmins on the vesicle membrane which triggers the FUSION of the vesicle membrane with the terminal membrane.
a pore opnes into the synapse and cations rush in and acetylcholine is released via exocytosis into the synaptic cleft
acetylcholine vesicle release is blocked by……
acetylcholine vesicle release is enhanced by…..
blocked by botulinum toxin
enhanced by black widow spider venom
acetylcholine binds and activates…..
cholinoreceptor
true or false
acetylcholine undergoes rapid deactivation by acetylcholinesterases
true
what are other cholinesterases with a lower specificity for acetylcholine?
butyrylcholinesterase
(pseudocholinesterase)
