Flashcards in Neurotransmitters Deck (56):
What is the difference between neurotransmitters and neuropeptides?
Neurotransmitters are small molecules which normally mediate fast synaptic signalling (contained in small, clear core synaptic vesicles).
Neuropeptides are large molecules that mediate slower synaptic signalling or moderate ongoing synaptic function (contained in large, dense core vesicles [also true for the monoamines]).
Name the difference in how neurotransmitters and neuropeptides are removed from the synaptic cleft.
Neurotransmitters are usually taken back up into the synaptic terminal and reused, neuropeptides are not taken back up, but instead leave the synaptic cleft through diffusion and degradation.
Name the five major classes of neurotransmitters and give some examples.
Neuropeptides (large molecules) - Substance P, endorphins, vasopressin, somatostatin.
Amino acids - glutamate, glycine, gamma-amino butyric acid (GABA).
Monoamines/Biogenic amines - noradrenaline, adrenaline, dopamine (these three are catecholamines), serotonin, histamine.
Gases - nitric oxide, carbon monoxide.
Other - acetylcholine.
What is co-transmission, and why is it important?
Neurons releasing more than one neurotransmitter. Co-transmission gives versatility to neurotransmission.
How does the preference of release of either the small (neurotransmitter), or large (neuropeptide) vesicles change with a change in the frequency of stimulation?
At a low frequency stimulation, the small vesicles are preferentially released over the large vesicles. At a high frequency of stimulation, both the small and large vesicles are released.
Name the 5 criteria for a chemical messenger to be a neurotransmitter.
1) The chemical must be synthesised and present in the neurone.
2) When released, the chemical must produce a response in the target cell.
3) This same response must be produced when the chemical is experimentally placed on the target.
4) There must be a mechanism for the removal of the chemical from the synaptic cleft after it has produced the response.
5) There must be specific receptors for the chemical present on the post-synaptic cell.
What are catecholaminergic neurones?
Neurones that contain noradrenaline, adrenaline, and dopamine.
Name the two types of neurotransmitter receptors and the difference between them.
Ionotropic receptors - contain an ion channel allostearically regulated by the neurotransmitter, and produce a fast response.
Metabotropic receptors - GPCRs which use intracellular signalling mechanisms to effect a change in ion channel gating, cell excitability, metabolic state, gene expression. The response is much slower.
Which is the most common neurotransmitter in the PNS?
Acetylcholine - present at the neuromuscular junction, and functions in the autonomic nervous system.
Name some things acetylcholine has a role in in the CNS.
1) Learning and memory
7) Sexual behaviour
Which neurones in the autonomic nervous system release acetylcholine?
Preganglionic, and postganglionic neurones of the parasympathetic system. Preganglionic neurones of the sympathetic system; and postganglionic neurones of the sympathetic system when the target cell is a sweat gland.
Acetylcholine is a critical neurotransmitter in learning and memory, so death of which cholinergic neurones contributes to Alzheimer's disease?
The cholinergic neurones from the basal forebrain nuclei, which project to the cortex and hippocampus.
Name the enzyme that produces acetylcholine from acetyl-coA and choline in nerve terminals.
Choline acetyltransferase (ChAT).
Name the enzyme that breaks acetylcholine down into acetic acid and choline in the synaptic cleft.
Which enzyme can be targeted to try and treat Alzheimer's disease?
Acetylcholinesterase. Inhibit it using drugs like donepezil (AChE inhibitor for CNS), and raise the level of ACh in the brain.
Where are nicotinic receptors found?
Neuromuscular junctions, autonomic ganglia, adrenal medulla, CNS.
What are the two types of nicotinic receptors?
Nn, found on postganglionic neurones, and presynaptic cholinergic terminals.
Nm, found on skeletal muscle endplates.
Where are muscarinic receptors found?
In peripheral tissues, in the autonomic nervous system, in the CNS. They are all G protein coupled receptors.
Which of the five subtypes of muscarinic receptors open K+ ion channels?
M2 and M4.
How is glutamate removed from the synaptic cleft?
Reuptake via glutamate transporters on the presynaptic membrane and on glial cells. Glutamine is then converted back to glutamate by the enzyme glutaminase.
What are the two neurotransmitters used in nociception?
Glutamate and Substance P.
Name 3 diseases thought to be caused by a lock of or dysfunction of glutamate transporters.
Motor neurone disease, epilepsy, Alzheimer's. A high concentration of extracelluar glutamate causes neurones to DIE.
What are the 3 subtypes of glutamate receptor?
AMPA (Na+ channel), NMDA (Ca2+ channel, and implicated in epilepsy), Kainate receptor.
What are the main inhibitory neurotransmitters in the CNS?
GABA and glycine.
What is the precursor of GABA and which enzyme converts it?
Glutamate, converted to GABA by Glutamic acid decarboxylase (GAD).
How are GABA and glycine removed from the synaptic cleft?
Reuptake via transporters on the presynaptic membrane and glial cells.
How are GABA receptors targeted by anxiolytics?
Benzodiazepines, barbiturates, ethanol, can all bind to an allostearic site on the GABA(A) receptor, which enhances the response of the receptor to GABA, to increase the amount of Cl- which flows into the cell, to hyper polarise the membrane.
In epilepsy, there is uncontrolled excitation in the brain, what can be used as an emergency treatment to treat epileptic seizures?
Where does most of the glycine in the CNS come from?
Derived from glucose via serine.
What are glycine receptors?
Ionotropic receptors linked to Cl- ion channels.
Where in the CNS does glycine mainly act?
Inhibition in the brainstem and spinal cord. (glycine is important for the inhibitory neurones of the anterior grey horn of the spinal cord)
Which potent convulsant blocks glycine receptors?
What does an inherited defect in glycine receptors cause?
Hyperekplexia (pronounced startle responses to tactile and acoustic stimuli, and hypertonia).
Name the catecholamines and say what group they all contain.
Noradrenaline, adrenaline, dopamine. All contain the catechol group (benzene ring with two hydroxyl groups).
What is the precursor of all the catecholamines?
Levodopa, converted to dopamine by decarboxylase. Dopamine can be converted to noradrenaline, which can be converted to adrenaline.
What's the difference between Uptake 1 and Uptake 2?
They both remove catcholamines from the synaptic cleft by reuptake, but Uptake 1 is found on the neuronal membranes, and Uptake 2 is on extra neuronal tissues.
How are catecholamines broken down?
Oxidation by monoamine oxidase (MAO).
What are the two MAO isozymes?
MAO(A) preferentially oxidises serotonin and noradrenaline. MAO(B) oxidises dopamine.
Name the 3 dopamine pathways in the brain.
Mesolimbic (reinforcement), mesocortical (planning) [from ventral tegmental nucleus], nigrostriatal (movement) [from substantial nigra].
What are the two subtypes of dopamine receptors?
D1 - like (GPCRs positively coupled to adenylate cyclase), D2 - like (GPCRs negatively coupled to adenylate cyclase).
What are the characteristics of Parkinson's?
TRAP - tremor of hand, rigidity of muscles, akinesia, posture.
What causes Parkinson's?
The degeneration of neurones from the substantial nigra to the striatum, so the direct pathway is not stimulated and the indirect pathway not inhibited.
How is Parkinson's treated?
L-dopa - increases dopamine levels in the substantial nigra neurones that are still alive, but can cause schizophrenia like symptoms.
Name a source of noradrenaline in the CNS.
Locus coeruleus in the pons - has a role in sleep/wakefulness, attention, feeding behaviour.
Which fibres in the PNS release noradrenaline?
Postganglionic sympathetic fibres (unless the target cell is a sweat gland).
A decrease in noradrenaline and serotonin activity is thought to lead to which disease?
An increase in noradrenaline activity is thought to lead to what?
Name a source of serotonin in the CNS.
The Raphe nuclei, in the midline of the midbrain, pons and medulla oblongata.
What is serotonin also known as?
5-Hydroxytryptamine (5-HT). It is synthesised from tryptophan.
Name some functions in the CNS that sertotonergic neurone have a role in.
Sleep, mood, emotional behaviour.
Describe the reuptake of serotonin.
Reuptake into the presynaptic neurone mediated by the serotonin transporter (SERT).
Which drugs inhibit SERT?
Most 5-HT receptors are metabotropic, which are ionotropic?
In which gland is 5-HT metabolised to melatonin?
How do MAO inhibitors work as antidepressants?
They prevent enzymatic breakdown of noradrenaline and serotonin so raise their levels.