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biol 125 > 4 - Neurotransmitters & main functions > Flashcards

4 - Neurotransmitters & main functions Flashcards

1
Q

Acetylcholine

A

• First neurotransmitter to be discovered in 1912
• Synthesis: Acetyl coA + Choline Acetylcholine (via Choline acetyl
transferase)
• Breakdown (on postsynaptic neuron):
Acetylcholine = Acetate + choline (via acetylcholinesterase)

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2
Q

Acetylcholine receptors

A
  • Acetylcholine binds to receptors on postsynaptic neurons
  • 2 main types: nicotinic (neuromuscular junction, brain, autonomic nerves) or muscarinic (smooth muscle, exocrine glands, brain)
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3
Q

agonists and antagonists

A

• Agonists are drugs that mimic the actions of the neurotransmitter
- Binding to the receptor = activation

• Antagonists are drugs that block the action of the neurotransmitter
- Binding to the receptor = no activation

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4
Q

cholinergic agonists and antagonists

A

Nicotinic receptors:
- agonist: nicotine (tobacco)
- antagonist: Curare (paralysis + poison)
Muscarinic receptors:
- agonist: muscarine (toadstool)
- antagonist: atropine (deadly nightshade)

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5
Q

Alzheimer’s disease

A
  • First described by Dr. Alois Alzheimer
  • Progressive onset of dementia, including problems with memory
  • Neuropathological changes include loss of brain weight, enlargement of ventricles, numerous senile plaques andq neurofibrillary tangles(NFTs) in the brain
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6
Q

Cholinergic death in Alzheimer’s

A
  • Acetylcholine is important for memory and attention

* Cholinergic neurons die early in AD

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7
Q

AChE inhibitors for treatment of AD

A

AChE inhibitors are one of only 2 approved drugs for the treatment of AD
• donepezil (1997)
• rivastigmine (2000)
• galantamine (2001)

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8
Q

Synthesis of catecholamines

A

Catechol group = phenol ring with -OH groups in 3 & 4 positions
• Synthesised from tyrosine, which is transported into the brain from the blood
• Catabolism involves enzymes monoamine oxidase (MAO) and catechol 0-
methyltransferase (COMT)

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9
Q

Dopamine signalling

A
  • 2 major families of dopamine receptors
  • D1-like: D1 & D5
  • D2-like: D2, D3, D4
  • D1-like are coupled to stimulatory G-proteins
  • D2-like are coupled to inhibitory G-proteins
  • All signal via adenylate cyclase & second messengers
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10
Q

Parkinson’s disease

A 
• First described in 1817 by James Parkinson
• Mean age of onset ~ 60 yrs
• Affects 1-2% over 65 yrs 
Characterised by: 
• muscle stiffness 
• slowness of movement 
• tremor at rest
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11
Q

Pathology of Parkinson’s disease

A
  • Degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta and loss of dopamine in the caudate-putamen
  • > 50% depletion of dopamine
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12
Q

Treatment of Parkinson’s

A
  • Motor symptoms of PD are alleviated by treatment with L-dopa which is transported into brain and converted to dopamine
  • Administration of a peripherally active Dopa decarboxylase inhibitor prevents premature conversion of L-dopa to dopamine
  • Inhibitors of COMPT and MAO-B can also be given to inhibit dopamine degradation
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13
Q

Synthesis & catabolism of serotonin

A
  • Synthesised from tryptophan by tryptophan hydroxylase and 5-hydroxytryptophan (5-HTP) decarboxylase
  • Broken down to 5-hydroxyindoleactic acid (5-HIAA) by MAO and aldehyde dehydrogenase
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14
Q

Serotonin signalling

A
  • 5-HT can bind to 14 different receptors which are all G-protein-coupled, except for 5-HT3 which is a ligand-gated ion channel
  • Some receptors are excitatory, others inhibitory
  • Action terminated mainly by reuptake from the synapse via the 5-HT transporter on the presynaptic neuron
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15
Q

SSRI treatment for depression & anxiety

A
  • Selective serotonin reuptake inhibitors (SSRIs) block the action of SERT = more serotonin at the synapse
  • Can help to reduce symptoms of depression, anxiety, OCD, PTSD, etc.
  • Examples:
  • citalopram (Cipramil)
  • escitalopram (Cipralex)
  • fluoxetine (Prozac or Oxactin)
  • paroxetine (Seroxat)
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16
Q

Amino acid transmitters

A
  • All are non-essential amino acids (made in situ from glycolytic and citric acid cycle intermediates)
  • Glutamate and aspartate are excitatory whereas glycine and GABA are inhibitory
17
Q

GABA receptors

A
  • GABA A = ionotropic receptor coupled to Cl− channel. Has modulatory binding sites for benzodiazepines, barbiturates, neurosteroids and ethanol
  • GABA B = metabotropic receptor coupled to Ca2+ and K+ channels via G proteins and second messenger systems
18
Q

Glutamate receptors

A
  • NMDA receptors bind glutamate, glycine, Mg2+, Zn2+ and polyamines. Form channels that are permeable to cations (Ca2+ > Na+ and K+)
  • Kainate and AMPA receptors interact only with glutamate and their specific agonists (Na+ and K+ > Ca2+)
  • mGluRs are G-protein coupled receptors and trigger a second messenger cascade (eight different types of mGluRs)
19
Q

Astrocytes buffer glutamate & GABA concentrations

A
  • Glutamate is removed from the synapse by astrocyte uptake via excitatory amino acid transporters (EAAT)
  • GABA is also taken up by astrocytes via GABA transporters (GAT)
  • Both glutamate and GABA are catabolysed in the astrocyte to glutamine, which is then transported to the neurons for re-use
20
Q

Many treatments target GABA & glutamate signalling

A

GABA receptor agonists are given for the treatment of seizures
• Memantine blocks the Mg2+ binding-site on the glutamate NMDA receptor
• Approved for use to treat Alzheimer’s disease in 2002

21
Q

Peptide neurotransmitters

A
  • Many types of small peptides (~100 known examples)
  • Most common type of neurotransmitter in the hypothalamus
  • Synthesised as large precursor proteins and transported to synaptic release site – activated by proteolytic cleavage
  • Slow postsynaptic effects
  • Actions terminated by extracellular proteases
  • Often co-released with other classical transmitters
  • Includes opioids - endorphins, enkephalins and dynorphins
  • Other examples are substance P, neurotensin, vasoactive intestinal peptide (VIP), etc.
22
Q

Other neurotransmitters

A

• Purines (ATP, GTP and others)
• Histamine
• Gases – nitric oxide (NO)
- NO is not stored in synaptic vesicles, but is made as required by an enzyme (NOS), from arginine
- NO simply diffuses from nerve terminals into adjacent cells and forms
covalent linkages to a multiplicity of targets, which may be enzymes or other targets
Inactivation presumably involves diffusion away

biol 125 (12 decks)

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