Lectures 17 & 18 Neurotransmitters and Neuromodulators

Question 1

What type of receptor are cholinergic N1 and N2 receptors?

Answer 1

ionotropic

Question 2

What is PDE? What is its action?

Answer 2

PDE- Phosphodiesterase

it breaks down cAMP into 5’ AMP

Question 3

What effector protein is activated by G-S?

Answer 3

Adenylyl cyclase (AC)

Question 4

What does Adenylyl cyclase do?

Answer 4

AC produces cAMP from ATP

Question 5

What enzyme can produce cAMP from ATP?

Answer 5

Adenylyl cyclase

Question 6

How is cAMP action terminated?

Answer 6

breakdown by phosphodiesterase (PDE)

Question 7

What are 2 ways that the concentration of cAMP can be regulated?

Answer 7

1. rate of synthesis by adenylyl cyclase (AC)

2. breakdown by phosphodiesteras (PDE)

Question 8

What does cAMP do? How is it made?

Answer 8

cAMP can activate and ion channel or another protein

It is made by adenylyl cyclase from ATP (AC is activated by a G-S protein)

Question 9

What happens to a g protein when GDP is exchanged for GTP?

Answer 9

it becomes activated

alpha subunit dissociates from beta-gamma subunit and they both go to interact with efferectors

Question 10

How are G-proteins inactivated?

Answer 10

the alpha sub-unit hydrolyzes the GTP back to GDP and the alpha, beta and gamma units again form a trimer (inactive)

Question 11

How does caffeine affect phosphodiesterase (PDE)?

Answer 11

decreases PDE thus increasing effects of cAMP

Question 12

How does G-C work?

Answer 12

activates guanylate cyclase to generate cGMP (similar to G-s that generates cAMP)

Question 13

How does G-i work?

Answer 13

decreases adenylyl cyclase activity and thus decreases cAMP production–>inhibition/modulation of ion channels (alpha-2 autoreceptors work in this manner-NE)

Question 14

What do G-q proteins activate?

Answer 14

phospholipase C (PLC)

Question 15

What 2 second messengers are produced as a result of PLC activation by Gq?

Answer 15

IP3 and DAG

Question 16

What does IP3 do?

Answer 16

causes release of calcium from the endoplasmic reticulum

Question 17

What does DAG do?

Answer 17

activates PKC

Question 18

What are the 3 second messengers produced as a result of Gq mediated activation of PLC?

Answer 18

IP3
DAG
Ca

Question 19

How does G-olf work?

Answer 19

causes an increase in cAMP which increases Na permeability–> depolarization of olfactory neurons

Question 20

What system is G-t found in? Is is inhibitory or excitatory?

Answer 20

transducin in the retina-visual system

inhibitory

Question 21

List the 6 g-protein cascades we discussed.

Answer 21

G-S
G-C
G-Q
G-OLF
G-T
G-i

Question 22

Of the 6 g-protein cascades we discussed which two decrease the amount of cAMP (inhibitory?)

Answer 22

G-t

G-i

Question 23

Of the 6 G-protein cascades we discussed, which two increase the amount of cAMP?

Answer 23

G-s

G-olf

Question 24

Which g-protein cascade releases internal calcium stores using IP3 as a 2nd messenger?

Answer 24

Gq

Question 25

Which g-protein cascade increases production of cGMP?

Answer 25

G-c

Question 26

What are the two major classes of Cholinergic receptors?

Answer 26

Nicotinic (2 subtypes) | Muscarinic (5 subtypes)

Question 27

Where are N-1 receptors found?

Answer 27

skeletal muscle

Question 28

Where are N-2 receptors found?

Answer 28

ANS

Question 29

Are cholinergic muscarinic receptors excitatory or inhibitory?

Answer 29

depends on location - GI Tract- excitatory (M1) - Heart-inhibitory (M2)

Question 30

What blocks the M1 receptor?

Answer 30

atropine

Question 31

What type of g-protein is the M1 receptor in the GI tract?

Answer 31

Gq- uses IP3 messanger system to increase gCa and cause depolarization-->excitation

Question 32

Are the nicotinic ACh-R ionotropic or metabotropic?

Answer 32

ionotropic

Question 33

Are the muscarinic ACh-R ionotropic or metabotropic?

Answer 33

metabotropic

Question 34

What can a lack of Norepinephrine cause?

Answer 34

depression

Question 35

How do tricyclics work?

Answer 35

by blocking NE re-uptake--> elevate mood

Question 36

How do MAO-Is work to treat depression?

Answer 36

inhibit monoamine oxidase (which breaks down NE) and thus increase NE in terminal

Question 37

Are dopamine receptors ionotropic or metabotropic?

Answer 37

all metabotropic

Question 38

What are the three catecolamines?

Answer 38

dopamine, epinephrine and norepinephrine (DA, E and NE)

Question 39

What neurotransmitter is involved in parkinson's disease?

Answer 39

dopamine decreased (death of cells in substantia nigra)

Question 40

How are D-1 and D-2 receptors different?

Answer 40

D-1 receptors are excitatory and cause and increase in cAMP (through Gs) D-2 receptors are inhibitory and cause a decrease in cAMP (through Gi)

Question 41

How many metabotropic GPCRs for dopamine have been identified?

Answer 41

4

Question 42

Which condition is marked by high numbers of D-4 dopamine receptors?

Answer 42

Schizophrenia (treated with phenthiazines like thorazine-block D-4 receptors- DA antagonist)

Question 43

How is dopamine cleared from the synaptic cleft?

Answer 43

Na-coupled transporter (blocked by cocaine and amphetamines)

Question 44

What is serotonin (5-HT) synthesized from?

Answer 44

tryptophan

Question 45

How many 5-HT receptors have been identified?

Answer 45

16 (15 GPCRS, 1 Ionotropic)

Question 46

What two illegal drugs cause a transient increase in 5-HT?

Answer 46

LSD and ectasy

Question 47

What does histamine control?

Answer 47

wakefulness, arousal

Question 48

What are the 2 main excitatory amino acid NTs in the brain?

Answer 48

glutamate and aspartate

Question 49

What are the 2 main inhibitory amino acid NTs in the brain?

Answer 49

GABA and Glycine

Question 50

What are the two opoid peptides?

Answer 50

endorphin and enkephalin

Question 51

What are the 2 ionotropic receptors for glutamate?

Answer 51

NMDA, AMPA, kainate

Question 52

Why is the gating of the glutamatergic NMDA receptor unusual?

Answer 52

it is both ligand and voltage gated (Mg stuck in channel-removed above -60mV)

Question 53

What is the major inhibitory NT in the brain?

Answer 53

GABA

Question 54

What are the two type of GABA receptors?

Answer 54

GABA-A and GABA-B

Question 55

How do GABA-A receptors function?

Answer 55

ionotropic receptor that increases gCl which opposes depolarization and results in inhibition

Question 56

How do GABA-B receptors function?

Answer 56

metabotropic receptors that act through the Gi mechanism to decrease cAMP, gCa and cause inhibition

Question 57

How do barbiturates and benzodiazepines such as valium work?

Answer 57

enhancing the effects of GABA on gCl ie. enhanced inhibitiion

Question 58

How does glycine work?

Answer 58

increases gCl-->inhibitory--> mostly works in the spinal cord

Question 59

What is familial startle disease caused by?

Answer 59

mutated glycine receptor

Question 60

What does strychnine block?

Answer 60

glycine channels- sometimes used by professional athletes to boost performance

Question 61

What is vasopressin aka?

Answer 61

anti diuretic hormone

Question 62

What is substance P most commonly involved in?

Answer 62

pain responsivity though recently implicated in some case of depression

Question 63

What are the gas nts?

Answer 63

NO and CO

Question 64

What does NO cause?

Answer 64

vasodilation of vascular smooth muscle (G-c pathway)

Question 65

What do NO and CO activate?

Answer 65

guanylate cyclase- Gc pathway

Question 66

How do ATP and adenosine act as NTs?

Answer 66

inhibitory NTs in the ANS

Question 67

What does viagra inhibit?

Answer 67

PDE- Phosphodiesterase- which breaks down cAMP and cGMP