Neurotransmitter Systems

Question 1

Acetylcholine (Cholinergic) :

• Synthesis:
• Moved into clear vesicles via ?
• Removed from synaptic trough via ? bound to post-synaptic cell membrane

Answer 1

• Choline and Acetate
• Vesicular Ach Transporter protein (VAchT)
• Acetylcholinesterase

Question 2

Acetylcholine (Cholinergic):
• Receptor Location
- M1 (neuronal): ↑ ? –>↑ ?

Answer 2

• ↑ IP3/DAG (Gq) –> ↑ Ca++

Question 3

Acetylcholine (Cholinergic):
• Receptor Location
- M2 (cardiac): ↓ ? –> ↑ ? efflux

Answer 3

• ↓ cAMP (Gi) –> ↑ K+ efflux

Question 4

Acetylcholine (Cholinergic):
• Receptor Location
- M3 (smooth m. of bronchi, vasculature; endothelial cells of vasculature
(NO): ↑ IP3/DAG (Gq) –> ↑ Ca++

Answer 4

• ↑ IP3/DAG (Gq) –> ↑ Ca++

Question 5

Acetylcholine (Cholinergic):
• Receptor Location
- M4 (presynaptic autoreceptor; striatum of basal ganglia): ↓ ?

Answer 5

↓ cAMP (Gi)

Question 6

Acetylcholine (Cholinergic):
• Receptor Location
- M5 (cerebrovasculature; dopaminergic neurons of basal ganglia): ↑ ?

Answer 6

↑ IP3/DAG

Question 7

Acetylcholine (Cholinergic):
• Nicotinic Receptors 
• Located at:
- 
- Synapse between ? and ?cells in autonomic ganglia

Answer 7

• Located at:

• NMJ
• Synapse between pre- and post-ganglionic cells in autonomic gangli

Question 8

2 major inhibitory amino acids

Answer 8

• GABA

- Glycine

Question 9

Which area has the least GABA of all?

Answer 9

Spinal Cord

Question 10

Roles of GABA

Answer 10

Multiple Roles but critical in:

• Consciousness
• Motor Control
• Vision (retina)

Question 11

GABA
• Synthesis
- From ?
- Important Enzyme:

• Transported into vesicles by ?
• Removed from synapse via ?
• 2 Forms:
  1. GAT1 - on the ?
  2. GAT2 - on ? cells surrounding the synapse

Answer 11

• Synthesis

• From GLUTAMATE
• Important Enzyme: GLUTAMATE DECARBOXYLASE (GAD)
• Transported into vesicles by Vesicular GABA Transporter protein (VGAT)
• Removed from synapse via GAT (GABA Transporter)
• 2 Forms:
  1. GAT1 - on the presynaptic terminal
  2. GAT2 - on glial cells surrounding the synapse

Question 12

If GAT1 (on the presynaptic terminal) takes the GABA up, the GABA is repackaged into ? as is.

Answer 12

vesicles

Question 13

If GAT2 (on the astrocytes) takes the GABA up, the GABA is converted to ? and released to the ?, where it will be taken up by the ? and recycled into ?.

Answer 13

• Glutamine
• ECF
• Presynaptic terminal
• GABA

Question 14

• Ionotropic (Cl conductance)
• Activation produces ipsp in adult neurons.

• Multiple binding sites
modulate:
- Benzodiazepine site 
- Ethanol 
- Certain steroids 
- These all potentiate.

Answer 14

GABA(A) Receptors

Question 15

• Metabotropic
• Gi/Go protein coupled.
• Activate a K+ channel (GIRK)
• Close down (inhibit) a Ca++ channel

• Located pre- and post-synaptically

• Presynaptic: regulate NT release
• Postsynaptic: inhibition of post-synaptic cell

Answer 15

GABA(B) Receptors

Question 16

Glycine:
• Found in:
- ?
-  ?
-  Much less in ?

Answer 16

• Found in:

• Spinal Cord (major)
• Brainstem (medulla)
• Much less in higher areas of CNS

Question 17

Glycine:

- Function ?

Answer 17

Function

- Mediates many spinal inhibitions

Question 18

Glycine:

- Production ?

Answer 18

Production:

- Unmodified amino acid

Question 19

Glycine:
- Removal from synapse:
?

Answer 19

Removal from synapse:

• GAT proteins (same as GABA)
• Recycling

Question 20

Glycine Receptor

• Ionotropic (Chloride)
• Influx of ? leads to ipsp
• ? and ? bind to it and potentiate
• ? binds to it and blocks it

Answer 20

• Influx of CHLORIDE leads to ipsp
• ETHANOL and GENERAL ANESTHETICS bind to it and potentiate
• STYCHNINE binds to it and blocks it

Question 21

2 Major classes of purines?

Answer 21

P1 and P2

Question 22

P1 (A receptors)

• ligand = ?
• Post-synaptic locations ?
• Pre-synaptic locations ?

Answer 22

• ligand = adenosine
• Post-synaptic locations
• Sleep induction
• General inhibition of neural function

• Pre-synaptic locations
- Inhibition of neurotransmitter release

Question 23

P2 receptor = ?

• Ionotropic
• Ligand: ATP
• Many subtypes

Answer 23

P2X

Question 24

P2 receptor = ?

• Metabotropic
• Ligand: ATP, ADP, UTP, UDP
• Gs/Gq coupled

Answer 24

P2Y

Question 25

Functions of purines?

Answer 25

* Learning & memory (co-release with EAA) | * Modification of locomotor pathways

Question 26

• These neurotransmitters are peptides made in the soma and transported down the axon via fast axonal transport. • Includes several transmitters: - ?

Answer 26

Peptide Transmitters Include: - The opioids - The tachykinins, including Substance P. - Cholecystokinin - Somatostatin - others

Question 27

• The opioids are a family of peptides that include: | ?

Answer 27

* The endorphins (endogenous morphines – we knew about morphine first). * The enkephalins * The dynorphins * Nociceptin

Question 28

Functions of the Opioids?

Answer 28

* Modification of nociceptive inputs (Cutaneous senses). | * Mood/Affect

Question 29

4 Precursor molecules of opioids?

Answer 29

• Proopiomelanocortinin (PCOM) - Β-Endorphins • Pro-encephalin - Tyr-gly-gly-phe-X - Met-enkephalin (X = methionine) - Leu-enkephalin (X = leucine) • Pro-dynorphin - 3 molecules of Leu-enkephalin - Dynorphin • Orphanin FQ --> nociceptin

Question 30

Synthesis of the opioids?

Answer 30

Standard protein synthesis in the cell body

Question 31

Removal from trough/cleft of the opioids?

Answer 31

• Probable reuptake • Enzymatic destruction - Enkephalinase - Aminopeptidiase

Question 32

Opioid receptor | - u- Receptor (mu) = ?

Answer 32

Metobotropic receptor

Question 33

***Opioid activation causes (u-receptor)?

Answer 33

* Analgesia * Respiratory depression * Euphoria * Constipation * Sedation

Question 34

Opioid Receptor: | Kappa (K) receptor =?

Answer 34

Serpentine

Question 35

Opioid (kappa) receptor produces: | - ?

Answer 35

* Analgesia ** * Dysphoria ** * Diuresis * Miosis

Question 36

Opioid Receptor | - Delta receptor = ?

Answer 36

Serpentine

Question 37

Opioid (delta) receptor produces ?

Answer 37

Produces analgesia** when activated.

Question 38

Opioid Receptor: • All opioid receptors are ? (serpentine) and activate second messenger systems with ligand binding. - All connect to ? proteins - Mu receptor: leads to an increase in ? efflux and hyperpolarization. - Delta- and Kappa-receptors: ~Decrease ? influx.

Answer 38

• All opioid receptors are METABOTROPIC (serpentine) and activate second messenger systems with ligand binding. - All connect to Gi/Go proteins - Mu receptor: leads to an increase in POTASSIUM efflux and hyperpolarization. - Delta- and Kappa-receptors: ~Decrease CALCIUM influx.

Question 39

Endocannabinoids: • Broadly distributed in the CNS • Basal ganglia functions: - ? • Spinal cord - ? • Cortex - ? • Hippocampus - ? • Hypothalamus - ?

Answer 39

• Basal ganglia - Mood - Motor performance • Spinal cord - Modulation of nociception • Cortex - Neuroprotection • Hippocampus - Memory formation • Hypothalamus - Control of body energy/hunger

Question 40

Endocannabinoids synthesis: - Derived from ? - Occurs in ?

Answer 40

- Membrane lipids (arachidonic acid) | - presynaptic terminal

Question 41

Endocannabinoid: • The CB1 receptor: - Found on pre-synaptic terminals of ? and ? releasing synapses - ? EAA and GABA release. - Via a ? coupled protein - ? and ? are equally effective.

Answer 41

- Found on pre-synaptic terminals of EAA and GABA releasing synapses - REDUCES EAA and GABA release. - Via a Gi coupled protein - ANANDAMIDE and 2-AG are equally effective.

Question 42

Endocannabinoid: CB2 receptor • Associated with ? * Location: ? * Action: ? * Special note: in the brain, activation of the CB2 receptor increases ?

Answer 42

CB2 receptor • Associated with IMMUNE SYSTEM • Location: - Microglia in brain - Gut - Immune system in general * Action: ANTI-INFLAMMATORY * Special note: in the brain, activation of the CB2 receptor increases β-AMYLOID REMOVAL.