Exam 2 - ACH and Serotonin

Question 1

What does the drug vesamicol do?

Answer 1

decreases the release of ACH from the terminal button

Question 2

Nicotinic receptors:

Answer 2

are found on muscle cells at the neuromuscular junction

Question 3

A specific marker for serotonin cells is:

Answer 3

tryptophan hydroxylase

Question 4

What are the two precursors to ACH synthesis?

Answer 4

choline and acetyl CoA

Question 5

What is the catalyst enzyme for ACH synthesis?

Answer 5

choline acetyltransferase - ChAT
- used to make acetylcholine and coenzyme A

Question 6

What is the name of the transporter protein that carries ACH into the vesicle? What drug blocks this transporter?

Answer 6

• vesicular ACH transporter protein (VACHT)
• vesamicol - decreases vesicular ACH and increases ACH in the cytoplasm

Question 7

What does venom from the black widow cause?

Answer 7

large release of ACH at peripheral synapses

Question 8

What does botulinum toxin do?

Answer 8

• inhibits ACH release at neuromuscular junctions
• causes nausea, vomiting, paralysis, asphyxiation
• also used for cosmetic purposes

Question 9

What can botox be used to treat?

Answer 9

• spasticity that comes after having a stroke

Question 10

What enzyme breaks down ACH? What does this breakdown result in? Does ACH have a reuptake mechanism?

Answer 10

• acetylcholinesterase (AChE)
• choline (reuptake blocked by hemicholinium) and acetic acid
• no - the only NT that does not have a reuptake mechanism

Question 11

What are the reversible inhibitors of AChE? Irreversible? Explain each.

Answer 11

• reversible:
  
  • physostigmine - crosses BBB, used to treat glaucoma
  • neostigmine - doesn’t cross BBB, used to treat intestinal tone
• irreversible:
  
  • sarin and soman - nerve gases, blocks breakdown of ACH

Question 12

Cholinergic system

Answer 12

• originates in the striatum and basal forebrain
• play an important role in motor control, cognition and memory

Question 13

192 IGG-Saporin

Answer 13

neurotoxin that destroys cholinergic neurons, but spares non-cholinergic neurons

Question 14

Alzheimer’s disease causes a significant reduction in _______ neurons.

Answer 14

cholinergic

Question 15

Alzheimer’s disease

Answer 15

• brain disorder/dementia characterized by loss of brain tissue mainly in the cortex and hippocampus, and beta-amyloid plaques and neurofibrillary tangles
• significantly low levels of ACH

Question 16

What are the stages of AZ?

Answer 16

1. mild - 2-4 years, individual is less energetic, minor memory loss, mood swings
2. moderate - 2-10 years, need assistance with complicated tasks, forget recent events and personal history, become more disoriented and disconnected from reality
3. severe - 1-3 years, inability to feed themselves, speak, recognize people and control bodily functions

Question 17

Nicotinic receptors (characteristics)

Answer 17

• ionotropic
• both subunits must be activated
• agonist is nicotine
• 5 protein subunits

Question 18

Poison curare

Answer 18

• nicotinic antagonist
• blocks cholinergic transmission, and causes paralysis and muscle relaxation

Question 19

Muscarinic receptors

Answer 19

• metabotropic
• main agonist is muscarine
• 5 subtypes
• important for reward

Question 20

Knocking out the M5 receptors reduced what?

Answer 20

the rewarding effects of morphine

Question 21

Muscarinic agonist

Answer 21

• pilocarpine, acrecoline
• mimic the effects of parasympathetic activation (salivation, pupil constriction, convulsions)

Question 22

Muscarinic antagonists

Answer 22

• inhibit parasympathetic actions, blocks memory
• atropine and scopolamine

Question 23

Serotonin synthesis

Answer 23

• precursor is tryptophan, which is catalyzed by tryptophan hydroxylase to make 5-HTP, which is then catalyzed by aromatic amino acid decarboxylase (AADC) to make serotonin

Question 24

Tryptophan brain entry

Answer 24

• in order to get more tryptophan, you need to eat more carbs
• usually received from food, so when deprived of food, tryptophan is no longer crossing the BBB as much, and its levels increase in the blood instead, rather than in the brain

Question 25

What transporter protein stores serotonin?

Answer 25

VMAT2, blocked by reserpine

Question 26

What drugs stimulate the release of serotonin?

Answer 26

• drugs similar to amphetamine: para-chloroamphetamine, fenfluramine, MDMA

Question 27

What does the serotonin/5-HT transporter do? What drugs inhibit this transporter protein? What is the transporter protein metabolized by? What is the end result of this?

Answer 27

• controls reuptake of serotonin
• SSRIs
• MAO
• 5-HIAA

Question 28

Serotonergic system

Answer 28

• majority of serotonergic neurons are in the raphe nucleus

Question 29

When are the neurons of the dorsal raphe nucleus most active?

Answer 29

• during active waking, which shows a coordination with activity and movement

Question 30

5,7, - DHT produces a lesion in the serotonergic system and shows what?

Answer 30

• that the serotonergic system is involved in changes in food intake, reproductive behavior, anxiety, and learning and memory

Question 31

5-HT1A receptors

Answer 31

• reducing CAMP synthesis by inhibiting adenylyl cyclase
• increases the opening of K+ channels, hyperpolarizing the membrane

Question 32

5-HT1A agonists

Answer 32

• buspirone, isopirone, and 8-OH-DPAT
• causes hyperphagia, and reduction of anxiety

Question 33

Serotonin and eating behavior

Answer 33

serotonin decreases eating behavior

Question 34

What happens if you genetically knock-out the 5-HT1A receptor in mice?

Answer 34

increase in anxiety

Question 35

5-HT2A receptors

Answer 35

• opposite of 5-HT1A
• activate the phosphoinositide second messenger system (increases Ca2+ and activates protein kinase C)

Question 36

5-HT2A agonist

Answer 36

• DOI
• produces twitching of the head in rats, and hallucinations

Question 37

5-HT2A antagonists

Answer 37

• ketanserin, ritanserin
• used to treat schizophrenia