Lecture 7 Part 3

Question 1

explain how norepinephrine is synthesized

Answer 1

tyrosine and sodium are transported into the nerve terminal by an A transporter

tyrosine hydroxylase catalyzes the conversion of tyrosine to Dopa, which then becomes DOPAMINE through Dopa decarboxylase

Dopamine enters a vesicle through VMAT in exchange for a hydrogen ion. there, it gets converted to NOREPINEPHRIN by Dopamine B-hydroxylase

Question 2

what can inhibit tyrosine hydroxylase?

Answer 2

metyrosine

tyrosine won’t be converted to Dopa and NE can’t be synthesized

Question 3

what can inhibit the transport of dopamine into a vesicle through VMAT transporter?

Answer 3

Reserpine

Question 4

explain the release of norepinephrine

Answer 4

released also through the influx of calcium and VAMPS/SNAPS

binds to ADRENOCEPTORS

Question 5

after NE has been synthesized and released, explain its potential fates

Answer 5

-usually recycled back into the nerve terminal through NET (norepinephrine transporter)

-can be released by diffusion and broken down (after binding adrenoceptors)

-can bind back to NE autoreceptor

Question 6

what inhibits the release of NE in vesicles by blocking VAMPS and SNAPS

Answer 6

bretylium and guanethidine

Question 7

what blocks the reuptake of norepinephrine through NET?
what is the result of this?

Answer 7

cocaine
tricyclic antidepressants

this causes NE to stay in the synaptic cleft for longer and binds to the postsynaptic neuron for a longer period of time

Question 8

in which cases is norepinephrine the final product?
in which cases is epinephrine the final product?
in which cases is DOPAMINE the final product?

Answer 8

NE in MOST sympathetic postganglionic neurons

in the adrenal medulla and certain areas of the brain - epinephrine

in dopaminergic neurons - ends with dopamine synthesis

Question 9

how is NE converted to epinephrine and where does this occur?

Answer 9

through Phenylethanolamine-N-methyltransferase

occurs mainly in adrenal medulla and some areas of the brain

Question 10

true or false

phenylethanolamine-N-methyltransferase is a phase 2 enzyme

Answer 10

true

Question 11

normally, what is the ration of norepinephrine to epinephrine

Answer 11

80% NE
20%E

Question 12

besides going through dopamine, explain another pathway of NE synthesis, starting from tyrosine

Answer 12

tyrosine is converted to tyramine by L-amino acid decarboxylase

Tyramine is converted to Octopamine by Dopamine B-hydroxylase

Octopamine is converted to NE through Hydroxylase from the liver

Question 13

can NE ever be released through a calcium INDEPENDENT process?

Answer 13

yes

indirectly acting and mixed sympathomimetics such as tyramine, amphetamines, and ephedrine

excellent substrate for monoamine transporter and are taken inside the nerve terminal and remove NE from vesicles and release it

Question 14

____________ inhibits monoamine oxidase and enhances NE and dopamine neurotransmission

Answer 14

Amphetamine

Question 15

what does amphetamine do in relation to NE?

Answer 15

inhibits monoamine oxidase and enhances NE and dopamine neurotransmission

Question 16

how many ways can noradrenergic transmission be terminated ? name them

Answer 16

2:

reuptake into the nerve terminal by NET or into other cells

simple diffusion away from the receptor site (eventually metabolized in the plasma or liver)

Question 17

what is the RATE LIMITING STEP in catecholamine synthesis?

Answer 17

the conversion of tyrosine to dopa by tyrosine hydroxylase

Question 18

the rate limiting step of catecholamine synthesis can be inhibited by…..

Answer 18

metyrosine

Question 19

what is VMAT?
what can inhibit it?

Answer 19

VMAT = vesicular monoamine transporter
-importer for catecholamines into the vesicle

can be inhibited by RESERPINE ALKALOIDS

Question 20

True or false

NET is partially responsivle for the termination of synaptic activity of norepinephrine

Answer 20

true

Question 21

the _______ and the endocrine system are integrated

Answer 21

ANS

Question 22

what is the function of aldosterone

Answer 22

to maintain fluid in the body

Question 23

what are autoreceptors?

Answer 23

presynaptic receptors that respond to the primary transmitter substance released by the nerve ending

part of negative feedback loop

Question 24

what are heteroreceptors?

Answer 24

regulatory receptors on nerve terminals that respond to many substances other than the primary neurotransmitter

Question 25

how do local anesthetics, tetrodotoxin, and saxitoxin affect neurotransmitter synthesis? name its site

Answer 25

they affect the propagation of an action potential by blocking voltage gated sodium channels and blocking conduction located in nerve axons

Question 26

explain what type of drugs inhibit transmitter synthesis and how

Answer 26

metyrosine - inhibits tyrosine hydroxylase and blocks catecholamine synthesis hemicholiniums -- blocks the uptake of choline, resulting in slow synthesis

Question 27

what is the site of hemicholiniums?

Answer 27

cholinergic nerve terminals membrane

Question 28

what is the site of metyrosine?

Answer 28

adrenergic nerve terminals adrenal medulla cytoplasm

Question 29

what drugs affect transmitter storage and how?

Answer 29

vesamicol - prevents the storage and depletes reserpine - prevents the storage and depletes

Question 30

explain the site of vesamicol and reserpine

Answer 30

vesamicol -- cholinergic terminals, VAT on vesicles reserpine - adrenergic terminals, VMAT on vesicles

Question 31

what drugs affect transmitter RELEASE? what is their site?

Answer 31

MANY DRUGS - nerve terminal membrane receptors. modulate the release of the transmitter w-conotoxin GVIA4 in particular works at nerve terminal calcium channels and thus reduces transmitter release botulinum toxin prevents the release of acetylcholine from cholinergic vesicles

Question 32

what is a-latrotoxin? what is its site and what does it do?

Answer 32

located at cholinergic and adrenergic vesicles affects transmitter release by causing explosive transmitter release

Question 33

name 2 drugs that PROMOTE neurotransmitter release where are they located?

Answer 33

located at adrenergic nerve terminals tyramine and amphetamine

Question 34

name drugs that inhibit the reuptake of NE through NET at adrenergic nerve terminals what is the effect?

Answer 34

cocaine tricyclic antidepressants SNRI antidepressants results in INCREASED NE EFFECT on the postsynaptic receptors

Question 35

what is the effect of NE on alpha receptors?

Answer 35

causes contraction

Question 36

what is the effect of phentolamine on alpha receptors?

Answer 36

PREVENTS the activation of alpha receptors

Question 37

name 2 drugs that act on alpha receptors and their function

Answer 37

norepinephrine binds alpha receptors and causes contraction phentolamine binds alpha receptors and prevents their activation

Question 38

name 2 drugs that bind adrenergic Beta receptors and their effect

Answer 38

isoproteronol - activates adenylyl cyclase propanolol - binds beta receptors and PREVENTS their activation

Question 39

explain the action of nicotine

Answer 39

binds nicotinic receptors and opens ion channels in the postsynaptic membrane

Question 40

what is the location of nicotinic receptors

Answer 40

nicotinic cholinergic junctions in autonomic ganglia and neuromuscular end plates

Question 41

explain the action of Tubocurarine

Answer 41

prevents the activation of nicotinic receptors at neuromuscular end plates

Question 42

name 2 drugs that bind muscarinic receptors and explain what they do

Answer 42

bethanechol - activates muscarinic receptors atropine - binds muscarinic receptors and PREVENTS their activation

Question 43

name the sites of bethanechol and atropine

Answer 43

muscarinic parasympathetic effector cells, such as smooth muscle and glands