Neuroreceptors and Ntts

Question 1

CRITERIA FOR CNS NEUROTRANSMITTERS

Answer 1

• Present in detectable quantities in the CNS
• Present in axon terminals of neurons
• Synthesized within the neuron
• Evidence of inactivation
  mechanisms in the vicinity of the synapse
• Act on RECEPTOR sites similarly to the natural activation of the synapse (EXCEPTION -> Nitric Oxide -> Gas that goes straight through PM)

Question 2

Fast Acting CNS Neurotransmitters

Answer 2

• Acetylcholine
• Glutamate and Aspartate
• GABA and Glycine

Question 3

CNS Biogenic Amines

Answer 3

• Dopamine (3-Hydroxytyramine)
• Norepinephrine (Noradrenaline-Arterenol) (noradrenergic)
• Serotonin (5-Hydroxytryptamine, 5-HT)
• Histamine

Question 4

BIOGENIC AMINES vs FAST ACTING NEUROTRANSMITTERS

Answer 4

FAST acting NTs are degraded much FASTER than biogenic amines

Temporal kinetics
-> it takes longer time to reuptake biogenic amine NTs

Spatial kinetics
-> because biogenic amine NTs are out in the synaptic cleft for a longer time (degraded more slowly) -> they have greater potential to activate receptors that are farther away from presynaptic neuron

There are differences in the types of receptors that the different NTs engage

Question 5

Point-to-Point Vs Overflowing Synapse

Answer 5

Point-to-Point -> NT binds to a nearby postsynaptic neuron

Overflowing synapse -> NT binds to distant receptors

Question 6

Ionotropic receptors vs. Metabotropic receptors

Answer 6

Ionotropic receptors

• > Ligand gated ion channels
• > FAST acting receptor (and usually Fast-acting NTs bind to Ionotropic receptors)

Metabotropic receptors

• > GPCRs
• > BOTH fast-acting NTs and Biogenic amines can use Metabotropic receptors

Question 7

Acetylcholine

Answer 7

• > FAST NT
• > typical NT of neuromuscular junction
• > Binds to Cholinergic receptors (two groups: 1) Nicotinic and 2) Muscarinic receptors)

Question 8

Types of Cholinergic Receptors

Answer 8

Acetylcholine can bind to BOTH

1) Nicotinic
2) Muscarinic

Question 9

Biochemical Responses mediated by Muscarinic Acetylcholine Receptors

Answer 9

Beta Adrenergic receptor (GPCR) for Norepinephrine
-> Upon binding NE, stimulatory Alpha subunit is activated and Adenylyl cyclase is activated to produce more cAMP

M2/M4 receptor (GPCR) for Acetylcholine

• > Inhibitory Alpha subunit causes inactivation of Adenylyl cyclase and reduced cAMP
• > through mechanisms that we don’t exactly know, this receptor can also affect flow through ligand-gated ion channels -> leads to more K+ influx

M125 receptor (GPCR) 
-> Acetylcholine binds and alpha subunit is activated -> more activation of adenylyl cyclase and increased cAMP production -> leads to stimulation of phospholipase C and eventually more Ca++ release

Question 10

Three Members of Glutamate Transporters:

Answer 10

1) Glutamate-aspartate transporter (GLAST)
2) Glutamate transporter-1 (GLT-1)
3) Excitatory amino acid carrier-1 (EAAC1)

GLT-1 and GLAST are expressed preferentially in glial cells. In contrast, EAAC1 is expressed predominantly in neurons.

A major role for glutamate transporters: limit the free concentrations of glutamate and aspartate in the extracellular space, thus preventing excessive stimulation of glutamate receptors and cell death.

It is likely that membrane depolarization during ischemic insult causes reverse transport of glutamate, or aspartate, out of glia and/or neurons.

Question 11

NMDA receptor

Answer 11

This receptor is the basis of learning and memory

Has a key feature -> Mg++ ions block the NMDA receptor channel ->

Long Term Potentiation -> the first time you drive, it’s really hard and you have to think about every little thing that you do -> but eventually this becomes a lot easier and you don’t even have to think about driving

Question 12

Accessory Proteins (like Homer)

Answer 12

In order to activate a receptor, the receptor has to be TURNED the right way in the PM
-> to make sure that the receptor is functional, you stabilize the receptor (with accessory proteins like PSD-95, which stabilizes NMDA receptors)

HOMER -> protein that is specific for Group I metabotropic receptor for glutamate

Question 13

NMDA Receptor Activation vs. AMPA Receptor Activation

Answer 13

NMDA receptor activation is SLOWER than AMPA receptor activation

Question 14

GABA Receptor

Answer 14

Inhibitory Receptor

Reason that GABA is Inhibitory NT
-> it is a channel for Chloride -> influx of Chloride into the cell causes the inside of the cell to become hyperpolarized

GABA receptor has different sites for different drugs:

• Barbiturate site
• Alcohol site

Question 15

Substantia Nigra

Answer 15

Site of the majority of Dopamine production (degenerated in Parkinson’s disease)

Question 16

Catecholamine Synthesis Pathway

Answer 16

Tyrosine -> L-DOPA -> Dopamine -> Norepinephrine -> Epinephrine

Rate limiting step = Tyrosine Hydroxylase [Tyrosine -> L-DOPA]
-> deciding factor of how much Dopamine, NE, Epinephrine we have in the system

Question 17

Serotonin Synthesis Pathway

Answer 17

Tryptophan -» Serotonin -> Melatonin

Question 18

Monoamine Storage and Release

Answer 18

Monoamines are concentrated in storage vesicles

Storage in synaptic vesicles is mediated by a single monoamine vesicular transporter (VMAT)
-> At least two VMAT isomers have been identified, VMAT1 in peripheral paracrine cells and VMAT2 in neurons

The action of monoamines released at the synapse is terminated by diffusion and reuptake into presynaptic nerve terminals by ligand-specific plasma membrane transporters

Monoamine receptors are GPCRs, belong to several families and exhibit several subtypes

Question 19

Dopamine Receptors

Answer 19

Are G-Protein Coupled