Neurotransmitters and neuropeptides Flashcards
What are monoamines and what is their structure?
• Monoamines- class of neurotransmitters o Monoamine neurotransmitters contain one amino group connected to an aromatic ring by a two-carbon chain
What are neurotransmitters?
Neurotransmitters- chemical signals released from a cell (usually from a synapse) to signal one or more other cells
What are different classes of neurotransmitters?
- Amino acids
- Peptides
- Quatemary amines
- Purinergics
- Lipid metabolites
- Biogenic amines
Give examples of amino acid neurotransmitters
• Amino acids
o Glutamate- excitatory neurotransmitter
o Glycine
o GABA- inhibitory neurotransmitter
Give examples of peptide neurotransmitters
o Opioids: enkephalins
o Vassopressin
o Somatostatin
Give an example of quatemary amine neurotransmitters
o Acetylcholine
Give an example of purinergic neurotransmitters
o ATP
Give an example of lipid metabolite neurotransmitters
o Anandamide
Give examples of biogenic amines and their different classes
o Catecholamines Noradrenaline Adrenaline Dopamine o Indoleamine Serotonin o Imidazoleamine Histamine
What is the general role of monoamines?
o Function in the brain to regulate cognitive processes such as emotion, arousal and certain types of memory
What CNS disorders do monoamine drugs treat?
o Drugs that alter monoamine neurotransmission are used to treat psychiatric and neurological disorders, including depression, anxiety, schizophrenia and Parkinson’s disease
Describe what monoamine neurotransmitters are usually synthesised from and how this synthesis occurs
o Synthesised from decarboxylated amino acids
o Synthesis is mainly catalysed by cytosolic enzymes
The type of enzyme present in a typical neuron is what determines what type of monoamine is produced and henceforth the function of the cell
What receptors do monoamines usually activate and why does this make them good drug targets?
o Monoamines mostly activate G-protein coupled receptors
Desirable drug target as means that slow metabotropic neurotransmission is being modulated, which is considered safer
Where are monoamines anatomically distributed?
o Characteristic anatomical distribution: synthesis is limited to a few restricted sub cortical or brainstem regions, which project to multiple cortical and limbic target regions
Describe the process of catecholamine synthesis
L-tyrosine-> through tyrosine hydroxylase (cytoplasmic rate limiting), L-dihydroxyphenylalanine (L-DOPA) is produced through addition of a hydroxyl group-> through aromatic L-amino acid decarboxylase (DOPA decarboxylase, cytoplasmic), dopamine is produced->through dopamine beta-hydroxylase (vesicular), noradrenaline is produced through addition of a hydroxyl group-> through phenylethanolamine N-methyl-transferase (PNMT, cytoplasmic), adrenaline is produced by addition of a methyl group
Describe the process of indoleamine synthesis
o Indoleamines
Both L-tryptophan and 5-HTP can cross the blood brain barrier, but not 5-HT
L-tryptophan-> through tryptophan hydroxylase (cytoplasmic, rate limiting), 5-Hydroxy-L-tryptophan (5-HTP) is produced-> through aromatic L-amino acid decarboxylase (DOPA decarboxylase, cytoplasmic), 5-hydroxytryptamine (5-HT, serotonin) is produced
How are monoamines stored and how do they get to that storage space?
o Active transport into vesicles via vesicular monoamine transporter (VMAT)
Transporter in the membrane of the vesicles and it is non-selective
• Any molecule with structural similarity to monoamines can pass through these transporters
o Stored as bound complex with ATP, protein (chromogranin-like), Ca2+, Mg2+ which prevents them from getting out of the vesicle
o The concentration of the neurotransmitter that gets stored in the vesicle is extremely high (About 1.1 M)
What causes monoamine release and how is it done?
channels
o Calcium enters the cell which promotes fusion of vesicles to terminal membrane
o Exocytosis of monoamines from their vesicles occur
o Note: some monoamines can also be released extrasynaptically
E.g. 5HT
What are the types of dopamine receptors and describe their role
o Dopamine receptors G-protein coupled receptors (GPCRs, metabotropic) D1-like (D1, D5) • D1-like mainly excitatory D2-like (D2, D3, D4) • D2-like mainly inhibitory
What are the types of adrenoceptors and describe their role and their differential affinity to adrenaline and noradrenaline
o Adrenoceptors G-protein coupled receptors (GPCRs, metabotropic) • Alpha-adrenoceptors o Alpha1, alpha2 • Beta-adrenoceptors o Beta1, Beta2 and Beta3 Adrenaline: affinity B2> B1/B3/alpha Noradrenaline: affinity alpha> B1>>B2
What are the types of serotonin receptors, their roles, their tropic type and their classification criteria
o Serotonin receptors
Classified (1992) according to:
• Cloned sequence
• Signal transduction mechanisms
• Pharmacological specificity
5HT1, 5HT2, 5HT3, 5HT4, 5HT5, 5HT6, 5HT7
Subtypes: 5HT1A, 1B, 1D, 1-like, (1E), 1F, 2A, 2B, 2C
5HT3 receptors are ionotropic, the rest are metabotropic
5HT1 receptors mediate inhibition, the rest mediate excitation
How does monoamine reuptake occur?
o Reuptake
Active transport into neurons via high affinity Na+ dependent membrane transporter proteins: DAT, NAT and SERT
Main mechanism for terminating monoamine synaptic action
How does monoamine degradation generally occur?
Cytoplasmic monoamines are broken down by monoamine oxidase (MAO) via oxidative deamination
Where is monoamine oxidase bound and what are its two isoforms? What do they degrade?
MAO is bound to mitochondria
MAO isoforms:
• MAO-A degrades 5-HT, NA, A and DA
• MAO-B degrades DA