Neurotransmitters Flashcards
What is a neurotransmitter?
Ligands/ chemical substances produced by neurons that transmit signals to target cell (nerves, muscle, glands) across a synapse.
The 4 properties of neurotransmitters?
- Synthesised and stored in vesicles in terminal boutons of presynaptic neuron ( end of axon)
- Released from presynaptic neurons
- Bind to specific post synaptic receptors
- Rapidly removed from synaptic cleft
How are NT removed from cleft ? And examples
- Diffusion
- Reuptake - repackaged to vesicles or into glial cells ( serotonin, GABA, glutamate, glycine)
- Inactivation by enzymes ( Ach)
7 categories of Nts? With examples
- Amino acids - GABA, Glycine, Glutamate
- Amines- Catecholamine, DA, NE, 5-HT, Histamine
- Neuropeptides- opioid peptides ( enkephalins, endorphins, dynorphin)
- Ach
- Lipids
- Nucleosides
- Gases - NO
3 actions of NTs? With examples.
- Excitatory - depolarisation of post synaptic membrane to
Promote action potentials
( Glu, ACh, Histamine, DA, NE/ NAd, Epi/ Ad ) - Inhibitory- hyperpolarization
(GABA, 5- HT,DA) - Modulatory
( DA, 5-HT, ACh, histamine, NE )
What is a NT receptor?
Genetically-coded proteins embedded in cell membrane
Types of NT receptor? With examples.
- ionotropic ( NT molecule bind to outside and channel open making it permeable to NA+, K+ or Cl-) ex. GABA
- metabotropic ( G-protein coupled / seven transmembrane receptors is a single protein winding thru cell membrane 7 times) ex. All monoamine receptors except 5-HT3
Metabotropic vs ionotropic receptors ?
Meta. Vs. Iono.
1. Slower 1. Works very fast
2. Longer lasting response. 2. Slow lasting response
3. No channel/ pore. 3. Has channel/ pore
How do G protein coupled receptors work ?
- NT molecule binds with receptor
- Receptor activates G protein
- a subunit breaks off from G protein and binds to ion channel and opens it
- Ions enter cell, produces postsynaptic potential
Or - a subunit activates enzyme that produces 2nd messenger
- Ion channel opens
- Ions enter cell nd produce postsynaptic potential
- 2nd messenger goes to nucleus / other parts of cell
4 NT Receptor properties and examples
- Each ligand has many subtypes of receptors
Ex. NE binds to a and B - Presynaptic receptors inhibit further release of NT
- Prolonged exposure to ligand causes most receptors to be desensitised
- Upregulation and downregulation of receptors
Five Locations of ACh secretion?
- motor neurons
- Autonomic nerves
- Pyramidal cells of motor cortex
- Basal ganglia
- Hippocampus
3 Functions of ACh?
- Regulate sleep cycle
- Essential for motor function
- Essential for cognitive function
3 types of ACh receptors with their location?
- Nicotinic- nAChR- autonomic ganglia , NMJ (excitatory so sodium influx)
- Muscarinic - M1 to M5- brain, heart, pancreas, smooth muscles ( inhibitory so inc potassium conductance or dec cAMP)
- Parasympathetic nerve endings - 2nd messenger cAMP
4 Common ACh blockers? And how they act?
- Curare - plant poison. (NMJ block)
- Botulinum toxin - food poison. (NMJ block)
- Atropine ( M receptor blocker)
- Alzheimer’s patients. ( loss of ACh neurons)
How are catecholamines formed ?
by hydroxylation & decarboxylation of AA tyrosine.
How are catecholamines removed ?
- Reuptake
- Enzymatic degradation - intracellularly or in cleft by MAO OR COMT
What is norepinephrine ? ( location, effect on body and behaviour)
Present in autonomic nerves (most sympathetic postganglionic nerve endings, Adrenal medulla) brainstem, hypothalamus, locus ceruleus of pons
• Increases blood pressure and heart rate
• Increases alertness, attention and wakefulness, control
the overall activity of the brain and the mood
• Mainly excitatory
What are norepinephrine receptor types? 2nd messenger ?
receptors –α1 α2 β1 β2 β3 second messenger: cAMP
– Norepinephrine- α and β (more on α)
– Epinephrine - α and β (more on β)
Effect of deficiency of NE?
Deficiency associated with attention deficit hyperactive disorder ADHD
What is Dopamine (DA)? (Location, effect)
Secreted by Adrenal medulla, Brain (Substantia niagra, Cortex-Corpus striatum,Hypothalamus) and neurons in basal ganglia
• Mainly inhibitory
• Involved in pleasure, reward mechanisms in brain,
motivation and important in coordinating movements
What are DA receptors?
receptors: D1, D2, D3, D4, D5
second messenger: cAMP
Effects of DA?
Increased levels associated with schizophrenia, alcohol/drug (cocaine, opium, heroin)abuse
low levels are associated with Parkinsonism
What is GABA? ( location , how it’s synthesised , significance )
Present in the basal ganglia , spinal cord, cerebellum & Cortex
• Main inhibitory NT of the brain
• Synthesized by Decarboxylation of glutamate by
the enzyme Glutamate decarboxylase(GAD)
What are GABA receptors?
– GABA A increase Cl- influx
– GABA B act via G proteins, increase K+ influx
Effect of GABA
Low GABA levels are associated with anxiety and epilepsy
What is glycine ?
main inhibitory NT in spinal cord
What is 5-HT ( location,function)?
Secreted by CNS brainstem neurons- Control emotion, mood and important in sleep ,also present in GIT, platelets & limbic system
5- HT receptors?
receptors: 5-HT 1, 5-HT 2, 5-HT3, 5 HT-4, 5HT5, 5-HT6,5- HT7
What is Glu?
main excitatory NT of brain & spinal cord
Glu receptors?
receptors: metabotropic receptors, LGIC- (kainate,
AMPA, NMDA ) NMDAR hippocampus- involved in
memory & learning
Effects of Glu?
Increased levels are associated with certain neurological diseases
What is neuromodulator ? with examples.
• Neuromodulators are not restricted to the synaptic cleft : modulate regions or circuits of the brain
• They affect a group of neurons, causing a modulation of that group
• Neuromodulators alter neuronal activity by amplifying or dampening synaptic activity
• eg. dopamine, serotonin, acetylcholine, histamine, glutamate
Heteroreceptor vs autoreceptor
Heteroreceptors respond to neurotransmitters, neuromodulators, or neurohormones released from adjacent neurons or cells (presynaptic ); they are opposite to autoreceptors, which are sensitive only to neurotransmitters or hormones released by the cell in whose wall they are embedded (postsynaptic).
