CNS Neurotransmitters and Receptors (Linger) - SRS

Question 1

What are the 4 main types of NT’s for the CNS?

Answer 1

• AA transmitters
• Small molecule transmitters
• Peptides
• Endocannabinoids

Question 2

What are the amino acid transmitters?

Which are excitatory?

Inhibitory?

Answer 2

1. Excitatory
   
   1. Glutamate
   2. Aspartate
2. Inhibitory
   
   1. GABA (gamma amino butyric acid)
   2. Glycine

Question 3

What are the small molecule transmitters?

Answer 3

1. Acetylcholine
2. Monoamines
3. Histamine

Question 4

So, monoamines are small molecule transmitters eh? What are the monamines we need to know?

Answer 4

• Catecholamines
  
  • Dopamine
  • Norepinephrine
• Serotonin (5-hydroxytryptamine, 5-HT)

Question 5

What are the peptide NT’s?

Answer 5

1. Opioids
2. Tachykinins
3. Many others

Question 6

What are the endogenous opiod NT’s?

Answer 6

• Enkephalins
• Endorphins
• Dynorphins

Question 7

What is the tachykinin we need to know?

Answer 7

Substance P

Question 8

What are the ten sites of drug action that allow alteration of synaptic transmission?

Answer 8

1. Action potential in presynaptic fiber
2. synthesis of transmitter
3. storage
4. metabolism
5. release
6. reuptake into the nerve ending or uptake into a glial cell
7. degradation
8. receptor for the neurotransmitter
9. receptor-induced increase or decrease in ionic conductance
10. retrograde signaling.

Question 9

What are teh three basic criteria that define classical NT’s?

Answer 9

• Localization - NT must be localized to the presynaptic terminal
• Release - The transmitter must be released from the presynaptic terminal in a calcium-dependent manner, concomitantly with presynaptic nerve activity
• Synaptic mimicry -
  
  • Exogenous application of the transmitter should mimic the action of presynaptic nerve stimulation
  • Pharmacological agonists and antagonists should mimic and block the transmitter action, respectively

Question 10

What NT’s are not synthesized or stored in the presynaptic terminal?

Answer 10

Retrograde messengers - e.g. endocannabinoids

Question 11

What are five examples of NT’s that activate ionotropic receptors from this DSA?

Answer 11

1. Glutamate
2. GABA
3. Acetylcholine
4. Glycine
5. Serotonin

Question 12

Metabotropic receptors indirectly modulate ion channels. What type of receptor are they?

Answer 12

GPCRs

Question 13

What is the major functional effect of metabotropic receptors?

Answer 13

signal amplification, which can be excitatory or inhibitory depending on the G protein activated and the downstream effector protein

Question 14

What are some of the key second messengers and signaling effectors mediated by metabotropic receptors?

Answer 14

1. Adenylate cyclase and cyclic adenosine monophosphate (cAMP)
2. Polyphosphoinositide products:
   
   1. Diacylglycerol (DAG)
   2. Inositol-triphosphate (IP₃)
3. Ion conductance (Ca⁺⁺, K⁺, Na⁺, or Cl^-)

Question 15

What are some examples of NT’s that activate metabotropic receptors?

Answer 15

1. Glutamate
2. GABA
3. Acetylcholine
4. Dopamine
5. Norepinephrine
6. Serotonin
7. Histamine
8. Neuropeptides
9. Endocannabinoids

Question 16

Glutamate receptors include ionotropic and metabotropic. What are the types of ionotropic receptors?

Answer 16

• Non-NMDA
• NMDA

Question 17

What are the non-NMDA receptors glutamate hits?

Answer 17

AMPA, Kainate

Question 18

What do AMPA receptors do?

Answer 18

Mediate the vast majority of excitatory synaptic transmission in the brain via ligand gated sodium/potassium channels. (some are also permeable to calcium)

Question 19

NMDA receptors are ligand gated sodium/calcium channels that are also highly calcium permeable. Overstimulation of these receptors is especially important in what conditions?

Answer 19

Ischemia and hypoxia d/t stroke mostly, where calcium influx via these receptors triggers apoptosis

Question 20

What are two non-competative agonists for the NMDA receptor that are used recreationally/illegally?

What do they do at low doses?

High doses?

Answer 20

PCP and ketamine

Low = hallucinations and delusions

high = dissociative anesthesia

Question 21

what do postsynaptic metabotropic glutamate receptors do?

Answer 21

Decreases K+ conductance; Increases IP3, DAG

Question 22

What do presynaptic metabotropic receptors for glutamate do?

Answer 22

1. Decreases Ca⁺⁺ conductance (INHIBITORY); Decreases cAMP

Question 23

how does glutamate contribute to migraines?

Answer 23

excessive glutamate release contributes to the cortical spreading depression implicated in the aura of migraine headache

Question 24

Excessively rapid or sustained firing of a relatively small group of glutamatergic neurons in one region of the brain may rapidly lead to successive excitation of ever larger numbers of glutamatergic neurons until a major region of the brain is evoked into a paroxysmal discharge.

This can cause what potential outcomes?

Answer 24

• Seizure
• prolonged seizures and stroke can lead to apoptosis

Question 25

What degerative disease may glutamate have a hand in? What does this allow for as far as tx options go?

Answer 25

AD - NMDA receptor antagonist memantine is used to treat moderate to severe dementia of the AD type.

Question 26

How is the NMDA receptor a "coincidence receptor"?

Answer 26

A single synaptic input results in the generation of a short-lasting excitatory postsynaptic potential (EPSP) that is mediated entirely by AMPA receptors. (B) When multiple inputs occur simultaneously, nerve depolarization removes the Mg⁺⁺ block in NMDA receptor channels and the same single synaptic input generates a longer-lasting EPSP that is mediated by both AMPA and NMDA receptors. Thus, the NMDA receptor can “sense” the activity in adjacent inputs.

Question 27

How is GABA inactivated?

Answer 27

1. terminated by rapid reuptake by several types of plasma membrane transporters; GABA is also taken up by glial cells

Question 28

What type of receptors are GABA_A?

Answer 28

Ionotropic

Question 29

What type of receptors are GABA_B?

Answer 29

Metabotropic

Question 30

What are some drugs that bind to GABA_A Receptors?

Answer 30

Benzodiazepines barbituates ETOH

Question 31

Benzodiazepines (e.g., alprazolam (Xanax), diazepam (Valium), midazolam (Versed), Clonazepam (Klonopin)) are used to treat what disorders? 4

Answer 31

1. generalized anxiety disorder, 2. panic disorders, 3. sedation 4. sleep disorders

Question 32

What are barbiturates used for? 2

Answer 32

Sedative-hypotics antiepileptics

Question 33

Glycine works via ligand gated Cl- channels. What is a toxin that inhibits its release?

Answer 33

Tetanus toxin

Question 34

What is an antagonist of glycin?

Answer 34

strychnine

Question 35

At what receptors does glycine act as a co-agonist with glutamate?

Answer 35

NMDA

Question 36

Parkinsons involves degeneration of dopaminogenic neurons in what structure primarily?

Answer 36

The striatum

Question 37

What is a disease state that involves increased DA activity?

Answer 37

Psychosis (schizophrenia), thus D2 receptor antagonists are the classic therapy.

Question 38

Cocaine abuse has what impact on DA?

Answer 38

Blocks DA uptake

Question 39

What do amphetamines do to DA?

Answer 39

Increase release

Question 40

Ventral tegmental DA pathways mediate the subjective effects of drugs of abuse in what pathway?

Answer 40

the reward pathway

Question 41

What are the receptor types for NE?

Answer 41

All metabotropic

Question 42

What does substance P do?

Answer 42

NT for sensory afferent neurons that mediate pain