Neurotransmitters Flashcards
What 4 criteria does a neurotransmitter need to satisfy?
- Synthesis: the NT must be made in the pre-synaptic neuron
- Storage: the NT must be stored pre-synaptically in vesicles (exception is NO)
- Release: NT must be released on demand
- Inactivation: NT must be inactivated
What can happen to the NT after it binds and activates post-synaptic receptors?
+ Enzyme activation
+ Diffusion
+ Re-uptake
What is a receptor?
A protein that is either in the plasma or inserted in the outer membrane of a cell
What is the relationship between the receptor and a NT?
+ The receptor binds to and is activated by a NT
+ Lock and key hypothesis
+ Most receptors types are activated by only one NT but there are families of receptors sensitive to a single NT. exceptions include co-agonists, constitutively active receptors
What are the neurotransmitter classifications by structure?
+ Amino acids (simple compound with carboxyl group and amino group)
+ Biogenic amines:
- catecholamines
- indolamines
+ Peptides
What are the different amino acid neurotransmitters?
+ Glutamate
- primary excitatory NT of CNS
- acts through calcium ions
+ GABA
- inhibitory
- aminobutyric acid
+ Glycine
- inhibitory
(Other AAs: Aspartate, proline, taurine, beta-alanine)
What are the different biogenic amine neurotransmitters (catecholamines)?
+ Norepinephrine
+ Epinephrine
+ Dopamine
What are the different biogenic amine neurotransmitters (indolamines)?
+ Serotonin
What are the different peptide neurotransmitters?
+ Encephalin
+ Endorphin
+ Dynorphin
(Others include: Substance P, neuropeptide Y, neurotensin, cholecystokinin)
Where are the amino acid neurotransmitters produced?
In the bouton
What are functions of NT glutamate?
+ Action at post synapse predominantly by opening cation (e.g Na+) channels
+ Inactivation is by re-uptake and is recycled to either glutamate or GABA
What is the term for neurons within or spanning hemispheres?
Intra and inter-hemispheric connections
What are the terms for neurons descending to the braintstem or spinal cord?
+ Corticobulbar tracts
+ Corticospinal tracts
What other receptors are also permeable to calcium ions?
+ AMPA
+ Kainate
+ NMDA
What type of transmission are kainate glutamate receptors involved in?
Fast synaptic transmission and synaptic plasticity
What type of transmission are NMDA receptors involved in?
Slow synaptic transmission
Which neurotransmitter is involved in memory, learning and cell death?
Glutamate
What is synaptic plasticity?
+ The process by which synapses are strengthened or weakened by feedback mechanisms
+ Basic process for storing long and short term memories
What is the result of excessive glutamatergic stimulation of NMDA receptors?
A large influx of calcium ions; through a variety of processes this can result in cell death known as EXCITOXICITY
Which neurotransmitters is involved in migraines?
Glutamate
What can happen in regards to excess excitation?
It can feedback on itself to cause uncontrolled waves of excitation over expanding areas in the brain
What do the results of excess excitation manifest as at first?
+ Begin as PARTIAL COMPLEX seizures (partial - not the whole brain, complex - due to an alteration of consciousness)
What can the partial complex seizures progress to, and what causes the progression?
Grand Mal seizures (involve the whole brain):
- if the waves of depolarisation become more uncontrolled
How are seizures treated, and what do the treatments do?
With BENZODIAZEPINES:
- increase the action of GABA and drugs like PHENYTOIN which increase inactivation (refractory) period between firings in voltage activated Na+ channels
Why do benzodiazepines increase the action of GABA?
+ They act on a separate receptor binding site on the GABAa receptor, compared to GABA
+ This binding site controls the ability of GABA to open the channel; more benzodiazepines bound => GABA can open the channel more often
+ Benzodiazepines therefore only enhance the action of existing GABA molecules
What are some features of GABA?
+ Principle inhibitory NT of the CNS
+ Made from glutamate
Where is GABA found?
+ Predominantly in the interneurons of the CNS
+ Neurons of the striatum and globus pallidus, where it modulates descending motor information
GABA acts at ligand gated chloride channels (not K+ channels). What is it inactivated by?
Pre-synaptic reuptake
Name disease resulting from GABAergic dysfunction
Huntington’s
What is the role of GABA in Huntington’s, and what is the treatment?
+ GABAergic neurons degenerate, which can lead to uncontrolled movement
+ Treatment: GABA mimetic
What are the effects of alcoholism on GABA, and what are the treatments?
+ Causes a change in GABA transmission such that withdrawal results in convulsive movements and seizures
+ Treatment: Benzodiazepines (Diazepam, temazepam) and phenytoin
For what are GABA agonies sometimes used?
+ Treatment of anxiety
+ Treatment of sleeplessness
+ Treatment of epilepsy
+ Anaesthetics (e.g propofol)
What are some features of glycine?
+ Second most common inhibitory NT of the CNS
+ Synthesised from serine
+ Predominant inhibitory NT in the interneurons of the spinal cord and brain stem but also present in the brain
What is glycinergic dysfunction thought to be the cause of?
Inherited mammalian myoclonus
- most are benign
- others are late symptoms of more serious diseases
What causes tetanus, and how does it do so?
+ Caused by a toxin from the bacteria clostridium tetani
+ It inhibits the release of glycine resulting in a shift of the excitation-inhibition balance
What are the mild and serious effects of tetanus/shifts in excitation-inhibition balance?
Mild effects:
- restricted to muscles in Webster by cranial nerves
Serious effects:
- loss of inhibition in the cerebra => epiform fits
What is the treatment for tetanus/shifts in the excitation-inhibition balance?
Injection of antitoxin which binds the toxin and benzodiazepines which boost GABAergic pathways
What are some features/functions of norepinephrine?
+ Aka noradrenaline
+ Sympathetic NT: inhibition
+ Used in treatment for:
- Parkinson’s
- ADHD
+ Agonsists:
- cocaine
- tricyclic antidepressants
+ Projects major centres of the brain
What are some features/functions of epinephrine?
+ Aka adrenaline
+ Peripheral hormone from adrenal medulla
+ Pharmacological target for cardiac and circulatory problems
What are some features/functions of dopamine?
+ NT and neuromodulator
+ Involved in pleasure, addiction and movement
+ Dopaminergic axons project to the majority of the CNS (excluding cerebellum)
+ Act at G-protein linked metabotropic receptors
Where are catecholamine NTs synthesised?
+ In the bouton
+ Inactivated principally by re-uptake
What are adrenoceptors?
G-protein linked metabotropic receptors
What NTs are involved in the fight or flight response (gut, heart, respiration etc)?
Epinephrine and norepinephrine
What does the brainstem in the CNS use norepinephrine to influence?
\+ Sleep \+ Wakefulness \+ Attention (via reticulum) \+ Feeding behaviour (via hypothalamus) \+ Involved in bi-polar disorder
What is the Locus Coeruleus?
The part of the brainstorm whose neurons project norepinephrinergic axons
How many different central systems is dopamine found in and what is it involved in?
+ 3 different central systems
- The control of movement
- Certain symptoms of psychiatric disease
- Regulation of the release of certain hormones
Control of hormone release is exerted by dopamine. Where does this occur, and what is the role of dopamine?
+ Anterior pituitary
+ Dopamine released into portal vessels by hypothalamic neurons
What is the role of dopamine in Parkinson’s?
Parkinson’s sufferers who experience tremors, muscle rigidity and bradykinesia or akinesia have DEPLETED dopamine in the MOTOR CO-ORDINATION CIRCUITS
What is the role of dopamine in schizophrenia?
+ Can be caused by an OVER PRODUCTION of dopamine in the Mesolithic system
+ Treatment with antipsychotics
How is dopamine related to addiction of drugs of abuse, decide, and certain behaviours such as sexual activity?
Dopamine works through the pleasure centres of the CNS located in the mesolimbic dopamine system
What are some features/functions of serotonin?
+ Neorons originate principally in Raphe nuclei in the brainstem
+ Project to the majority of the brain and brainstem
+ Large family of both excitatory and inhibitory receptors, in the CNS & PNS
+ Modulates a range of NTs such as glutamate, GABA and dopamine
+ Functions associated with sleep, anxiety, depression and mood swings
What is serotonin dysfunction (reduction) associated with, and how can it be treated?
+ Associated with depression and obsessive compulsive disorder (OCD)
+ Treatment: fluoxetine (Prozac a 5-HT re-uptake inhibitor)
What are the receptor agonists involved in the serotonergic systems (often exploited by drug users) and what do they do?
+ LSD
+ Psilocybin
+ Mescaline
Inhibiting mono amine catabolism generally with MAOIs (monoamine oxidative inhibitors)
OR
Inhibiting serotonin re-uptake
=> increases 5-HT levels
What are examples of psychostimulants?
+ Amphetamines
+ Ecstasy
What are features of amphetamines?
+ Cause release of amines such as NA, 5-HT and dopamine
+ Also inhibit re-uptake of NA, 5-HT and dopamine thus causing enhanced activation of these receptors
What are features of ecstasy?
+ Amphetamine analogue: methylenedioxymethamphetamine or MDMA
+ Has numerous actions but its major effect is by causing the release of and preventing re-uptake of 5-HT
Which peptide NT is involved in Pain transmission
Substance P
Which peptide NTs are all implicated in schizophrenia?
+ Neuropeptide Y
+ Neurotensin
+ Cholecystokinin
Which NTs are associated with the perception of pain?
Endorphins and encephalins
What are the features/functions of endorphins and encephalins?
+ They act as opitate receptors in the brain and spinal cord where they are the endogenous ligand
What are some examples of opiates?
\+ Morphine \+ Codeine \+ Pethidine \+ Methadone \+ Diamorphine (heroin)
What does taking opiates lead to?
+ Down regulation of opiate receptors throughout the CNS
+ This causes opioid tolerance and increased intake
What is the result of there being opioid receptors in the limbic system (and the periaqueductal grey)?
+ Opiates affect emotional perception as well as pain
+ Emotional element to withdrawal avoidance
To whom is naxalone given, and what is its purpose?
It is given to withdrawing heroin addicts to reduce symptoms
What is naxalone?
An opiate receptor agonist
Give an example of an ester NT?
Acetylcholine (ACh)
+ An unusual NT but first one discovered
+ Used as a standard setter for defining NTs
What are features/functions of the NT- acetylcholine?
+ Principle excitatory NT
+ Found in both CNS and PNS
Where do the neurons of ACh project to?
The hippocampus & the cortex: essential for the formation of new memories and learning
What is associated with ACh dysfunction (reduction)?
Alzheimer’s disease
Which drugs act on AChs receptors?
+ Nicotine (drug of abuse)
+ Muscarine (agonist)
+ Atropine (antagonist)
+ Tropicamide (antagonist to dilate pupils during surgery)
What do anticholinesterases prevent?
The breakdown of ACh
What are some examples of anticholinesterases?
+ Insecticides (DDT)
+ Nerve gasses (Sarin)
Alzheimer’s treatments: Donepezil (aricept)
What is Korsakoff’s psychosis?
The diet of an alcoholic often leads to a thiamine deficiency causing famage to the thalamus and the mammillary bodies
What are the syptoms of Korsakoff’s psychosis?
+ Amnesia
+ Confabulation
+ Lack of insight
+ Apathy
Are there treatment options for Korsakoff’s psychosis?
The cells involved are cholinergic and partial recovery can sometimes be achieved by using anticholinesterases
