neurotransmitters Flashcards
what are neurotransmitters?
chemicals that transmit the signals of neurons
-not all chemicals produced by neurons are neurotransmitters
what does a chemical need to do to be considered as a neurotransmitter?
-Be synthesised and stored (generally in synaptic vesicles) in the presynaptic neuron
-Be released by the presynaptic axon terminal
-Produce responses in the postsynaptic cell,they function at the synapse
state the different structures of a typical synapse
-presynaptic terminal
-mitochondria
-secretory granules
-synaptic cleft
-synaptic vesicles
-active zone
-postsynaptic density
what is the presynaptic terminal?
-the end of the axon that forms the synapse (the conc of mitochondria is greater here)
what does the mitochondria do?
provides energy for the synaptic transmission
what are the secretory granules?
cell organelles which contain chemical (usually neuropeptides) which are released from the axon terminal to activate receptors on surrounding neurons
what is the synaptic cleft?
the area between the presynaptic terminal and postsynaptic regions (the space within a synapse)
what are the synaptic vesicles?
small spheroid cell organelles in which neurotransmitters are packaged
-this protects the neurotransmitters from degradation by surrounding enzymes, the release of neurotransmitters occurs by the fusing of the vesicles with the presynaptic membrane and releasing the contents
what is the active zone?
the part of the presynaptic regions where synaptic vesicles dock and are released
what is the postsynaptic density?
a region of the postsynaptic membrane, full of receptors
what are the chemicals at the presynaptic terminal of a typical synapse?
-neurotransmitters(proteins) and the enzyme (proteins) required for their synthesis
-vesicular transporters
-reuptake transporters
-degradative enzymes
what are vesicular transporters?
proteins which transport the neurotransmitter unto the synaptic vesicles
what are reuptake transporters?
proteins which take or transport the released neurotransmitter back into the presynaptic terminal
what are degradative enzymes?
they break down any free neurotransmitter
what are the chemicals at the postsynaptic region of a typical synapse?
-receptors=the proteins through which the neurotransmitter relays its signals or effects (can be presynaptic swell)
-secondary messengers (biochemical pathways which are initiated following the binding of the neurotransmitter to receptors
how do neurotransmitters function?
-all neurotransmitters(located presynaptically) function by binding to specific proteins
(receptors) which can be located pre or postsynaptically
-these activated receptors then cause a change in the function of the postsynaptic neuron, this can either be:excitation or inhibition of the postsynaptic neuron
what are agonists and antagonists?
agonists=agents(neurotransmitters/drugs) that bind to receptors
atangonists=agents that block receptors and prevent agonists from binding to their specific receptors
how do different classes of pharmacological agents work?
by either being an agonist or antagonist at various receptor systems
what are the two main types of receptors?
-ionotropic receptors
-metabotropic receptors
what are inotropic receptors?
proteins embedded in the cell membrane that form pores or channels for passing different ions e.g Na,Ca,Cl between the inside and outside of the neuron
how do ionotropic receptors work?
-When the agonist binds to these receptors the channels open and allow the movement of these ions into the neuron
-this movement of charge creates electrical currents and change the electrical potential of the inside of the cell-changes its excitability
contrast ionotropic receptors and metabotropic receptors..
-ionotropic receptors mediate fast synaptic neurotransmission, their activation results in the passage of ions whilst metabotropic receptors mediate slow synaptic neurotransmission, their activation leads to intracellular metabolic pathway signalling
what are metabotropic receptors?
-receptors that belong to a family of G-protein coupled receptors, these receptors are proteins embedded in the cell membrane but do not form pores or channels for the passing of ions, they are instead couples to intracellular regulatory proteins/enzymes
how to metabotropic receptors work?
-The binding of the agonist to these receptors initiates an intracellular biochemical cascade which = increase/decrease of other intracellular proteins or calcium levels which leads to neuronal excitation
-These receptors requires a number of biochemical pathways so the effects take much longer
what are the major neurotransmitters?
-Amino acids in which there are:
Gamma-aminobutyric (GABA)
Glutamate (Glu)
Glycine(Gly)
Amines
Acetylcholine(ACh)
Dopamine (ACh)
Epinephrine
Histamine
Norepinephrine (NE)
Serotonin (5-HT)
what is the major excitatory neurotransmitter throughout the nervous system?
Glutamate it is expressed in almost all brain regions
The binding of glutamate to its receptors causes excitation of neurons,this makes them more likely to fire action potentials
what are the classes of glutamate receptors?
-ionotropic (NDMA,AMPA,Kainate)
-Metabotropic(called mGluR,8 different sub-classes)
describe the synthesis of glutamate
-glutamine is converted to glutamate(glut) by enzyme glutaminase and glut is packaged into the synaptic vesicles for release
-alternatively,glutamine synthesised by the transamination of aspartate (asp) by the enzyme transaminase
-after glut is related from the axon terminal it is taken up by the glia and converted back into glutamine which is then transported back to the axon terminal for conversion back to glutamate
what glutamate transporter proteins is glutamate in the glia and neurons uptake by?
GLT-1,GLAST,EAAC1
what is the role of glutamate in brain function?
-it is important for different forms of learning memory, enhancing memory and cognition
what can dysregulation of glutamate activity lead to?
-excessive excitability of neurons which can cause things like:seizures, epilepsy,excitotoxity in stroke,NDMA antagonist of drugs of abuse (ketamine), NDMA impairment shown in SZ
what is the major inhibitory neurotransmitter in the brain?
GABA-the binding of GABA to its receptors (GABA-R) results in the inhibition of neuronal activity, this decreases the activity of the neurons making them less likely to fire an action potential
what are the classes of GABA receptors?
GABA-A ionotropic
GABA-B-metabotropic
GABA-C
describe the synthesis of GABA…
the synthesis of GABA happens by glutamate being converted to GABA by the enzyme glutamic acid decarboxylase
what do benzodiazepines do?
enhance the activity of GABA
state the agents that bind to benzodiazepine sites
-flunitrazepam
-zolpidem
-abecamil
state the members of neuromodulatory neurotransmitters…
-acetycholine
-noradrenaline
-seratonin
-dopamine
how do neuromodulatory neurotransmitters differ from glutamate and GABA?
-they are expressed only in select populations of neurons in specific brain regions, whereas glutamate/GABA are expressed throughout the whole brain
-this allows for functional specialisation of certain brain regions or centres
what are the major dopamine nuclei?
-substantia nigra
-ventral tegmental area
-hypothalanmus
how many dopamine receptors are there and name them?
-there are 5 in total named-D1,2,3,4,5
-they are all metabotropic and cause exception depending on the G-proteins
what is the role of dopamine in the brain?
-motor coordination
-motivation
-reward seeking
-cognition
-nausea+vomiting
-hormonal
state the different agonists and antagonists for the dopamine receptors
D2-agonist=Bromocriptine
antagonist=haloperidol
D4-antagonist-clozapine
what is the major noradrenergic nuclei?
the locus coeruleus
what are the different noradrenergic receptors?
-Alpha 1&2
-Beta 1,2,3
-they are all metabotrpic
-they cause exception or inhibition depending upon the G-proteins they are coupled to and their location (pre or postsynaptic)
what is the role of noradrenaline in the brain?
-arousal-fires action potentials when we are sleeping to wake us up, regulates arousal
state the different agonists and antagonists acting on the noradrenergic receptors…
alpha 1-agonist=phenylephrine,antagonist=Prazosin
alpha 2-agonist=clonidine,antagonist=prazosin
what neurotransmitter is there a lack of in people with Alzheimer’s disease?
there is a lack of acetylcholine
what are the major acetylcholine nuclei in the CNS?
-nucleus basal
-medical septal nucleus and diagonal band
-pedunculopontine nucleus (in the brainstem)
state the two classes of acetylcholine receptors…
-nicotinic(ionotropic)-has 17 subunits
-muscarinic (metabotropic)-has 5 subtypes M1-5
what is the role of acetylcholine in the brain?
-cognition
-motor activity
-mood
state the agonists and antagonists for the muscarinic cholinergic receptors
agonist=carbachol
antagonist=atropine
what is the main serotonin producing nuclei in the CNS?
-the raphe nuclei in the midbrain and pons
how many subclasses does the serotonin receptors have?
7-they are all metabotropic except 5HT3,which is ionotropic
what is the role of serotonin (5HT) in the brain?
-sleeping
-pain
-emotion
state the agonists and antagonists for the serotonin receptors…
5HT1A-antagonist=WAY 100135
5HT1B-agonist=sumatriptan
5HT4-agonist=metoclopramide
look at images for dopamine synthesis and serotonin synthesis
