Chemical Transmission in the Nervous System Flashcards Preview

Cardiovascular & Respiratory Pharmacology (Karen) > Chemical Transmission in the Nervous System > Flashcards

Flashcards in Chemical Transmission in the Nervous System Deck (40)
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1
Q

Action potentials are propagated down the neuron by the opening of

A

Na+ channels

tf these are a target for blocking NT release

2
Q

How is excitation targeted pharmacologically at synapses?

A

blocking of Na+ channels prevents AP propogation and tf NT release

3
Q

How is NT synthesis targeted pharmacologically at synapses?

A

targeting enzymes that produce NT

provide substrate or block activity

4
Q

How is NT storage targeted pharmacologically at synapses?

A

vesicle storage and release

5
Q

How is NT metabolism targeted pharmacologically at synapses?

A

enzymes that degrade NT

6
Q

How is NT release targeted pharmacologically at synapses?

A

fusion of vesicles with membrane to release contents into synaptic cleft

7
Q

How is NT degradation targeted pharmacologically at synapses?

A

enzymes that degrade NT; reuptake of NT by pre or post-synaptic membranes

8
Q

How are receptors targeted pharmacologically at synapses?

A

agonists or antagonists for NT receptors; prejunctional receptors can alter NT release (e.g. a2-aR limits NA release)

9
Q

The somatic nervous system is ________ and innervates

A

voluntary

skeletal muscle and overlying skin

10
Q

the parasympathetic nervous system is _______ and innervates

A

involuntary (ANS)

heart, glands, and smooth muscle

11
Q

the sympathetic nervous system is _______ and innervates

A

involuntary (ANS)

heart, blood vessels, glands (including sweat, adrenal)

12
Q

What is unique about the SNS innervation at the adrenal gland?

A

it releases ACh rather than NA to stimulate adrenaline release

13
Q

What are the two main chemical neurotransmitters of the peripheral nervous system?

A

ACh and NA

14
Q

How is ACh synthesized?

A
  • choline receptor on neurons transports dietary choline
    • acetyl-CoA from mitochondria via choline acetyltransferase –> ACh
  • ACh transported into vesicles via a carrier
  • drugs can modulate synthesis and storage but are of limited clinical use
15
Q

How is NA synthesized?

A
  • tyrosine –> neurons via transporter
  • broken down by tyrosine hydroxylase –> L-DOPA (L-dihydroxyphenylalanine)
  • broken down into dopamine by DOPA decarboxylase
    • dopamine can be the terminal product, or
    • broken down by dopanine beta-hydroxylase to NA in synaptic vesicles
  • synthesis and storage can be modulated by drugs
    • ​L-DOPA precursor drug can +dopamine production
    • enzyme blockers can -dopamine and tf -NA synthesis
16
Q

How is adrenaline synthesized?

A
  • in adrenals, NA is converted to adrenaline
  • via PNMT (phenylethanolamine-N-methyl transferase) in secratory vesicles
17
Q

What is the anatomical configuration of the ANS?

A

two fibres:

pre-ganglionic fibres from the CNS

post-ganglionic fibres from the autonomic ganglia

18
Q

What is the anatomical configuration of the somatic NS?

A

one fibre

CNS to skeletal muscle (alpha motor neuron)

19
Q

What is the anatomical structure of the sympathetic nervous system?

A
  • short pre-ganglionic fibres
  • ganglia located in sympathetic chain near SC
  • long post-ganglionic fibres
  • integration and modulation of responses
20
Q

What is the anatomical structure of the parasympathetic nervous system?

A
  • long pre-ganglionic fibres
  • short post-ganglionic fibres
    • ganglia close to tissue, sometimes within
21
Q

What are co-transmitters?

A
  • released with the dominant NTs ACh and NA from ANS neurons
  • e.g. ATP in sympathetic nerves releasing NA can act on purine receptors to fine-tune responses downstream
22
Q

How is ACh inactivated?

A
  • by degredation to prevent constant activation of post-synaptic receptors
  • degraded by acetylcholinesterase anchored to the post-junctional membrane
    • some ACh binds to cholinergic receptors and acitvates the post-synaptic membrane
    • other ACh binds AChE for degradation
  • tf degradation can be modulated by drugs
23
Q

How is NA inactivated?

A
  • by uptake
  • taken back into the releasing neuron (high-affinity uptake 1)
    • repackaged for subsequent signalling episodes
  • taken into post-synaptic neuron/tissue (low-affinity uptake 2)
24
Q

What is the neurotransmitter of the somatic nervous system?

A

ACh

released by upper motor neurons onto nicotinic receptors of the alpha motor neurons

alpha motor neurons relay stimulus by releasing ACh onto nicotinic receptors of muscles

causes excitation

25
Q

What is the main neurotransmitter of the PSNS?

A

ACh

preganglionic nerves release ACh onto nicotinic receptors at the ganglion

acts on nicotinic receptors of postganglion neurons

postganglionic neurons then release ACh on muscarinic receptors

26
Q

What is the main neurotransmitter of the sympathetic nervous system?

A

noradrenaline and adrenaline*

preganglionic to postganglionic is ACh acting on nicotinic receptors

postganglionic nerves synapse via adrenergic receptors using NA or A*

*except at sweat and adrenal glands where ACh is used

27
Q

What is the neurotransmitter of ganglionic transmission?

A

ACh

28
Q

ACh acts on (receptors)?

A
  • Nicotinic receptors (ligand-gated ion-channel)
    • ANS preganglionic synapse & Somatic postganglionic synapse
  • Muscarinic receptors (GPCR)
    • PSNS postganglionic synapse
29
Q

NA acts on (receptors)?

A
  • alpha and beta adrenoceptors (GPCRs)
    • SNS postganglionic synapse
30
Q

Atropine

A
  • muscarinic antagonist
31
Q

Curare

A
  • nicotinic antagonist
32
Q

What is the effect of blocking muscarinic receptors on ACh?

A

ACh can act on ganglionic synapses in ANS or sweat, adrenal glands

e.g. ACh causing vasodilation (usually via NA & A in the SNS)

33
Q

Alpha-adrenoceptors are located in

A

blood vessels

34
Q

Beta-adrenoceptors are located in

A

blood vessels and heart

35
Q

Adrenaline

A
  • activates alpha and beta-adrenoceptors
  • increases HR and BP
36
Q

Phenylephrine

A
  • a1 adrenoceptor agonist (smooth muscle of blood vessels)
    • increases BP, lesser effect on HR (beta)
  • nasal decongestant
37
Q

Isoprenaline

A
  • beta agonist
    • heart - causes +HR
    • BV SM vasodilation - causes -BP
38
Q

How do ligand-gated ion channel receptors function?

A
  • ligand e.g. ACh for nicotinic AChRs binds to receptor
  • changes its structure, allows ions into cell
    • e.g. Na+ enters cell, causes AP generation and propagation
39
Q

How do GPCRs function?

A

e.g. muscarinic AChRs, alpha and beta-adrenoceptors

  • 7 transmembrane proteins that bind to G-proteins (Guanine nucleotides)
  • activates enzymes yielding a downstream response
40
Q

What is the structure of the nicotinic ACh receptor?

A
  • 5 subunits
    • each has isoforms
    • arrange in different subtypes of NicRs found in different tissues (e.g. muscle, ganglionic, CNS)
  • has extracellular, transmembrane, and cytoplasmic regions