Neurotransmitters and Receptors

Question 1

criteria for CNS neurotransmitters

Answer 1

1) present in detectable quantities in the CNS
2) present in axon terminals of neurons
3) synthesized within the neuron
4) evidence of inactivation mechanisms in vicinity of the synapse
5) act on receptor sites similarly to the natural activation of the synapse

Question 2

name 5 fast acting CNS neurotransmitters

Answer 2

acetylcholine (NMJ)
glutamate (excitatory)
aspartate (excitatory)
GABA (inhibitory)
glycine (inhibitory)

Question 3

name 4 CNS biogenic amines (aka Monoamino NTs)

Answer 3

Dopamine
Norepinephrine
Serotonin
Histamine

Question 4

elimination of biogenic amines

Answer 4

reuptake
slower (last longer, can travel farther)

Question 5

elimination of fast acting neurotransmitters

Answer 5

degradation
No reuptake.

Acetylcholinesterase inactivates ACh at synapse

Question 6

spatial/temporal kinetics of biogenic amines vs fast acting NTs

Answer 6

BA: travel farther (available for longer before they are eliminated via reuptake)
OVERFLOWING SYNAPSE

FA: inactivated quickly, so act locally (eliminated before can travel far) POINT-TO-POINT

Question 7

postsynaptic receptors of biogenic amines vs fast acting NTs

Answer 7

BA: multiple step mechanism, takes longer

FA: channel, very fast

Question 8

ionotropic receptors

Answer 8

Fast.
Ligand binds, channel immediately opens.

Used by fast acting NTs

Question 9

metabotropic receptors

Answer 9

GPCR
Ligand binds, G protein dissociates, 2nd messengers activated.
Slower.

Used by both fast acting NTs and biogenic amines.
(it is the ONLY type of receptor that BA use)

Question 10

nicotinic receptor

Answer 10

For ACh.
In CNS.
IONOTROPIC.

Cations flow into cell, generate AP

Question 11

muscarinic receptor

Answer 11

For ACh.
At effector.
GPCR/METABOTROPIC.

Question 12

Beta-adrenergic receptor

Answer 12

Activated by NE
Type of metabotropic receptor.
Activation causes increased cAMP.

Question 13

M2/M4 AChR

Answer 13

Muscarinic receptor.
Metabotropic.
Inhibitory.
Decreases cAMP produced.

Question 14

how to avoid a null effect with B-adrenergic and M2/M4 receptors

Answer 14

1) differential NT release [controls which one is activated]

2) expression of one type of receptor over the other.

Question 15

stimulation of phospholipase C

Answer 15

Activated by M1.3.5 mAChR.
PLC –> PIP–> IP3 –> Ca++ increase.

Increased Ca++, then increased likelihood of AP

Question 16

major role for glutamate transporters

Answer 16

Limit free concentrations of glutamate/aspartate in extracellular space –> prevent excessive stimulation of glutamate receptors and cell death

Question 17

3 major glutamate transporters (and where they are expressed)

Answer 17

GLAST: glutamate-aspartate transporter
-expressed in glial cells

GLT-1: glutamate transporter
-expressed in glial cells

EAAC1: excitatory amino acid carrier
-expressed in neurons

Question 18

There are large amounts of Glu. How is brain death/overstimulation avoided?

Answer 18

Glial cells produce myelin sheath to isolate neuron from CSF

Question 19

functional classes of ionotropic glutamate receptors

Answer 19

NMDA
AMPA
Kainate

Question 20

functional classes of metabotropic glutamate receptor subtypes

Answer 20

Class I: IP3, Ca++
Class II: cAMP
Class III

Question 21

Long Term Potentiation (LTP)

Answer 21

NMDA receptor.

Main cellular pathway for learning.

Question 22

NMDA receptor

Answer 22

Glutamate receptor.
Has Mg++ cork blocking the channel.
Need frequent mechanical stimulation to dislodge Mg cork.
Once dislodged, Na/Ca can enter.

Question 23

stabilization of glutamate receptors in membrane is accomplished by…

Answer 23

Ampore (sp?) proteins.
Specific to receptor subtype.
Either facilitate or inhibit receptor trafficking.

Ex: Homer, PSD-95, GRIP

Question 24

NMDA component of transmission

Answer 24

Glutamate.
Slow rise, slow decay.

Fast acting, but the slower one (compared to AMPA)

Question 25

AMPA component of transmission

Answer 25

Glutamate.
Fast rise, fast decay.

Fast acting, and the faster one (compared to NMDA).

Question 26

Glutamate is [excitatory/inhibitory?], and is also a precursor to _________.

Answer 26

Glutamate is EXCITATORY, and is also a precursor to GABA (gaba is inhibitory; this helps keep excitatory NTs in check)

Question 27

GABA transaminase

Answer 27

connects GABA to TCA cycle

“GABA Shunt”

Question 28

GABA(A) receptor

Answer 28

Multiple recognition sites –> many effects.

Cl- enters, lowers resting potential. Inhibitory.

Question 29

norepinephrine cell bodies sit in ________

NE projections to _________

Answer 29

norepinephrine cell bodies sit in LOCUS COERULEUS (hind brain)

NE projections to medial forebrain bundle (MFB) is main one, but many diffuse projections.

Question 30

dopamine cell bodies sit in _________

dopamine projections to _____

Answer 30

dopamine cell bodies sit in VTA/A10, or substantia nigra (SN)

dopamine projections to striatum, accumbens, prefrontal cortex

Question 31

pathway associated with parkinsons

Answer 31

Nigra-striatal pathway.

Nigra –> striatum.
Dies in parkinsons

Question 32

pathways associated with addictive disorders

Answer 32

VTA/A10 –> accumbens

VTA/A10 –> prefrontal cortex

(dopamine)

Question 33

serotonin CNS pathways

Answer 33

Cell bodies in coeruleus/hind brain.
Diffuse projections (many places).

similar to NE, unlike dopamine

Question 34

catecholamine biosynthetic pathway

Answer 34

Precursor: tyrosine.
Rate-limiting step: tyrosine hydroxylase.

Tyr –> L Dopa –> Dopamine –> NE –> Epi

Question 35

serotonin biosynthetic pathway

Answer 35

Precursor: tryptophan

Serotonin is turned into melatonin in pineal gland.

Question 36

serotonin

Answer 36

indolamine.
monoamine
biogenic amine

Question 37

storage in synaptic vesicles is mediated by a single _________

Answer 37

monoamine vesicular transporter (VMAT)

Question 38

monoamine receptors are ______

Answer 38

monoamine receptors are GPCRs