Chemical transmission in the CNS Flashcards
Which receptors does NA act on in the sympathetic NS?
a and b adrenoceptors
What is the major NT in the sympathetic NS?
NA
What is the major NT in the parasympathetic NS?
Ach
Which receptors does Ach act on in the parasympathetic NS?
Muscarinic receptors
Which receptors does Ach act on in the somatic NS?
Nicotinic receptors
What is the major NT in the somatic NS?
Ach
Briefly describe the requirements for chemical neurotransmission?
Synthesis/storage of NTs Release of NTs Inactivation of NTs Receptors for NTs
What is required for synthesis and storage of NTs?
Vesicles
What is required for release of NTs?
Na and K channels Ca influx
What are the two broad mechanisms of NT inactivation?
Reuptake Degradation
What are the two major receptor types found at synapses?
Postjunctional and prejunctional
What is the trigger for the release of NT from neurons?
Na/K mediated APs > which causes Ca influx > exocytotic release of vesicle
How are prejunctional/presynaptic receptors important in transmission?
At high concentrations of NT, NT can bind for reuptake This can act as negative feedback to regulate NT
What is the key process for inactivation of NA?
Neuronal uptake
What is the secondary mechanisms for inactivation of NA?
Metabolism via MAO Extraneuronal uptake via MAO and COMT
Describe the action of cocaine in relation to NA?
Blocks neuronal uptake of NA > increased activation of receptors
Describe the action of amphetamine and ephedrine in relation to NA?
Are substrates for carrier and displace NA > reduced reuptake of NA
Describe how cocaine differs from amphetamine and ephedrine in its mechanism of action?
Cocaine blocks reuptake receptor Amphetamine and ephedrine act as substrates and displaces NA
Which characteristic of cocaine and amphetamines allows them to access their central targets?
Lipid soluble > can cross BBB
Which particular functions is NA associated with?
Stimulant effects Mood Appetite Cardiovascular
What is the estimate for the number of NTs that act in the CNS?
40
Describe the pathway for NA synthesis?
What is the precursor for adrenaline synthesis?
NA
How do neurons that synthesise adrenaline differ from those that do not?
Presence of enzymes that are able to convert NA to adrenaline
Why do some neurons stop at dopamine synthesis, rather than progress on to synthesising NA and adrenaline?
They lack the converting enzymes
How do noradrenergic and dopaminergic differ in their distribution in the CNS?
The noradrenergic neurons are more widespread, whereas the dopaminergic neurons are more discrete
How does the importance of dopamine differ in the CNS and PNS?
Very important in multiple CNS pathways
Less important in PNS, mostly a precursor to NA
List some of the pathways in which dopamine is involved in the CNS?
Movement
Behaviour
Dependence
Pituitary function
Apart from NA, which other NTs can cocaine block reuptake of?
Dopamine
Serotonin
Which of the NT actions is linked to the dependence effect of cocaine?
Dopamine
Which of the NTs is most strongly linked to the sense of euphoria, wellbeing and appetite effects?
NA
Serotonin
Why were the NA and serotonin mechanisms the lead for developing antidepressant drugs?
Linked to sense of wellbeing
Why were dopaminergic mechanisms avoided when developing antidepressant drugs?
Linked to dependence
Why can cocaine be used as a local anaesthetic?
Blocks Na channels
Can a synapse be both inhibitory and excitatory in the CNS?
No
Can NTs in the CNS be both excitatory and inhibitory?
Yes
How can some NTs be both excitatory and inhibitory in the CNS?
Depends on which receptors are present and which part of the brain you are in
Which receptor types are present in the CNS?
Ligand-gated ion channels (eg. nicotinic and GABA A)
GPCRs (muscarinic, a&b adrenoceptors)
What are post-synaptic receptors in the dendritic region important in determining?
AP generation and modulation
What are pre-synaptic receptors at the axon terminals important regulating?
NT release
What is the predominant role of tyrosine kinase and cytoplamic/nuclear receptors in the CNS?
Neuronal survival, rather than function
TAKE HOME MESSAGES
More than one NT usually involved
One NT usually involved in many pathways
