Neurotransmitters

Question 1

Amino acid neurotransmitters

Answer 1

Include glutamate and GABA

Question 2

Glutamate

Answer 2

The main excitatory neurotransmitter of the CNS

Stored in synaptic vesicles, release of these vesicles is Ca2+-dependent

Synthesised from glucose (from the Krebs cycle) or glutamine (from glial cells)

Glutamine is converted to glutamate by glutamine synthase

Question 3

Glutamate receptors

Answer 3

• NMDA = pre- & post-synaptic
• AMPA = post-synaptic
• Kainate = pre- & post-synaptic

Question 4

NMDA receptor

Answer 4

Has 7 subunits and several binding sites, an ion channel and modulatory sites

The ion channel is permeable to Ca2+ and Na+

The channel is blocked by Mg2+

Glycine is required as a co-factor for NMDA activation

Question 5

NMDA antagonists

Answer 5

NMDA antagonists bind to the receptor site of the NMDA receptor and have no effect

These hence inhibit the NMDA receptor

Question 6

Glycine antagonists

Answer 6

Glycine antagonists bind to the glycine binding site on NMDA receptors and have no effect

Since glycine is required for NMDA activation, this inhibits the receptor

Question 7

NMDA-channel blockers

Answer 7

NMDA channel blockers bind to a modulatory site on the NMDA receptor and block the ion channel

This inhibits the receptor

Question 8

Limitations of NMDA drugs

Answer 8

NMDA inhibitors have been prescribed by strokes, epilepsy and schiozphrenia

They have had disappointing results because the NMDA receptor is very abundant throughout the CNS, leading to lots of side effects

Question 9

GABA

Answer 9

The main inhibitory neurotransmitter in the CNS

Modulates other systems by inhibiting action potentials bu allowing chloride ions into the neuron, causing it to become hyperpolarised

Synthesised in GABAergic neurons from glutamate via the enzyme glutamic acid decarboxylase (GAD)

Question 10

GABA receptors

Answer 10

• GABA(A) = ligand-gated chloride channel

- GABA(B) = GPCR

Question 11

GABA(A) receptor

Answer 11

A pentamer with several binding sites that modulate activity and a Cl- channel

A particular modulatory site increases activity of the receptor by facilitating channel opening

Ligands for the modulatory site include ethanol and anaesthetic agents

Question 12

GABA antagonists

Answer 12

GABA antagonists bind to the primary receptor site and have no effect

This inhibits the receptor

Question 13

GABA(A) Modulatory site antagonists

Answer 13

Modulatory site antagonists bind to the modulatory site and have no effect

This inhibits the receptor because there is no ‘extra help’ in opening the channel

Question 14

Benzodiazepine agonists

Answer 14

Benzodiazepine agonists bind to the modulatory site to increase channel opening

This stimulates the receptor

Question 15

Monoamine neurotransmitters

Answer 15

Monoamine neurotransmitters include noradrenaline, dopamine, serotonin and acetylcholine

They are diffuse modulatory systems and reach many neurons

Associated with higher brain functions

Question 16

Noradrenaline

Answer 16

Released from the locus coeruleus

Associated with arousal, memory, attention, stress, cognitive control, emotions and neuroplasticity

Implicated in depression, anxiety and Parkinson’s disease

Degraded by MAO enzymes

Question 17

Adrenoceptors

Answer 17

Mediate the effects of noradenaline

All adrenoceptors (with the exception of B3) are expressed in the CNS

• a2 = auto-receptors
• B1 = cortex, striatum, hippocampus
• B2 = cerebellum

Question 18

Dopamine

Answer 18

Release from the ventral tegmential area (VTA)

Implicated in Parkinson’s disease, schizophrenia and ADHD

Synthesised from L-tyrosine in dopaminergic neurons

Broken down by MAO enzymes

Question 19

Dopamine receptors

Answer 19

All GPCRs

• D1 = post-synaptic, Gs coupled
• D2 = pre- & post-synaptic, Gi/o coupled

Question 20

Serotonin

Answer 20

Released from the Raphe nuclei

Involved in mood, memory processing, sleep and cognition

Implicated in depression, migraine, anxiety, OCD, schizophrenia and drug abuse

Synthesied from tryptophan

Degraded by MAO enzymes

Wide variety of receptors

Question 21

Acetylcholine

Answer 21

Released from the nucleus basalis

Involved in learning, short-term memory and motor control

Implicated in Parkinson’s disease, Alzheimer’s disease and Huntington’s disease

Question 22

Acetylcholine receptors

Answer 22

Muscarinic receptors are GPCRs and can be excitatory or inhibitory

Nicotinic receptors are ionotropic