Chemical Messengers and Excitotoxicity

Question 1

Difference between ionotropic and metabotropic NTs

Answer 1

Ionotropic = FAST — increase conductance to certain ions by binding ligand-activated channels

Metabotropic = SLOW — act to alter membrane properties via second messenger (often GPCRs)

Question 2

What are the 5 biogenic amine (monoamine) NTs

Answer 2

Catecholamines = epinephrine, norepinephrine, dopamine

Histamine
Serotonin

Question 3

Synthesis of catecholamines from tyrosine and RL step

Answer 3

Tyrosine —> L-DOPA (RL step) (requires tyrosine hydroxylase)

L-DOPA—> dopamine —> NE —> Epi

NE—> Epi requires PNMT

Question 4

Dopamine is stored in vesicles in neurons. ____ work to move dopamine, epi, etc. into specialized storage vesicles

Answer 4

VMATs

Question 5

Predominant mechanism for inactivation of Epi released by adrenal medulla, but also present in CNS

Answer 5

COMT

Question 6

Which NT’s neurons are located in locus ceoruleus and project to nearly every part of CNS?

Answer 6

Norepinephrine

Question 7

Functions of NE

Answer 7

Crucial to waking up and awareness

Question 8

_____ is used by a small fraction of neurons in the CNS and is primarily released by adrenal medulla

Answer 8

Epinephrine

Question 9

Where are the neurons that produce dopamine?

Answer 9

Substantia nigra

Ventral tegmental area of midbrain

Question 10

4 major systems that use dopamine

Answer 10

Substantia nigra — motor

Mesolimbic — VTA to nucleus accumbens. Central to pleasure, reward, addiction

Mesocortical — VTA to frontal cortex. Attention, high-level consciousness

Tuberinfundibular — hypothalamus to AP. Supresses release of prolactin

Question 11

Where is histamine found

Answer 11

Tuberomammillary nucleus (TMN) of posterior hypothalamus

Question 12

Function of histamine

Answer 12

Wakefullness

Question 13

Which histamine receptors mediate neuronal effects?

Answer 13

H1 and H2

Question 14

What degrades histamine

Answer 14

Diamine oxidase

Question 15

Serotonin neurons are located where?

Answer 15

Raphe nuclei

Question 16

Derivation of serotonin

Answer 16

Tryptophan —tryptophan hydroxylase—> 5HTP (RL)

5HTP —5-HT decarboxylase—> serotonin

Question 17

Function and metabolism of serotonin

Answer 17

Controls attention and mood; involved in depression

Metabolized by MAO enzyme after uptake

Question 18

How many serotonin receptors are there? Are they metabotropic or ionotropic?

Answer 18

7

All are metabotropic associated with GPCR signaling except 5-HT3 which is ionotropic

Question 19

Function of 5-HT2A

Answer 19

Smooth muscle contraction

Question 20

Function of 5-HT3

Answer 20

Vomiting

Question 21

Function of 5HT6

Answer 21

High affinity for several antidepressants

Question 22

Function of 5HT2C

Answer 22

Plays a role in controlling normal body weight and preventing seizures

Question 23

Central location of acetylcholine (cholinergic NT)

Answer 23

Pons
Midbrain
Motor cortex

[peripheral locations = autonomics, NMJ]

Question 24

Location of ACh neurons

Answer 24

Basal forebrain complex, which includes septal nuclei and nucleus basalis

[others originate in pontomesencephalotegmental cholinergic complex]

Question 25

Function of ACh

Answer 25

Learning, memory, producing consciousness, voluntary motion, REM sleep

Question 26

Transport mechanism for ACh from cytosol into vesicles

Answer 26

VAChT

Question 27

Where is acetylcholinesterase found?

Answer 27

Bound to post synaptic cell membrane

Question 28

Which ACh receptors are ionotropic vs. metabotropic?

Answer 28

Nicotinic receptors are ionotropic Muscarinic receptros are metabotropic

Question 29

Inhibitory amino acids

Answer 29

GABA | Glycine

Question 30

Location of GABA

Answer 30

Cortex, cerebellum (higher brain centers)

Question 31

Synthesis of GABA

Answer 31

Glutamate —glutamate decarboxylase—> GABA

Question 32

GABA tranmission is limited by ______. It is catabolized by __________ enzyme into succinic semialdehyde (SSA)

Answer 32

Reuptake; GABA-transaminase

Question 33

GABA receptors

Answer 33

GABA(A) = most prevalent, conducts chloride (IONOTROPIC), benzodiazepine receptor GABA (B) = GPCR (METABOTROPIC), results in increased K+ conductance or decreased Ca conductance

Question 34

Main inhibitory NT in spinal cord

Answer 34

Glycine

Question 35

3 opioid peptides

Answer 35

Endorphins Enkephalins Dynorphins

Question 36

4 types of receptors for opioids

Answer 36

Mu = analgesia, increases K efflux Kappa = analgesia, decreases Ca influx Delta = analgesia, decreases Ca influx Nociceptin = hyperalgesia