Pharmacology of Peripheral Neural Transmission (ANS function)

Question 1

What is the outflow of the sympathetic nervous system?

Answer 1

T1-L3

Question 2

What is the outflow of the parasympathetic nervous system?

Answer 2

• Cranial outflow: [III], [VII], [IX], [X]
• Sacral outflow: S2-S4

Question 3

What are the effects of sympathetic stimulation on the heart?

Answer 3

• ↑ Heart rate
• ↑ Contractility
• Mediated by β₁ receptors

Question 4

What are the effects of parasympathetic stimulation on the heart?

Answer 4

• ↓ Heart rate
• ↓ Force of contraction
• ↓ Conduction velocity through AV node
• Mediated by M₂ receptors

Question 5

What are the effects of sympathetic stimulation on vascular smooth muscle?

Answer 5

• Heart: Contraction (α₁ > α₂)
• Skeletal muscle: Relaxation (β₂)
• Viscera, skin, brain: Contraction (α₁ > α₂)
• Erectile tissue: Contraction (α)
• Salivary gland: Contraction (α)
• Veins: Contraction (α₁ > α₂)

Question 6

What are the effects of parasympathetic stimulation on the lungs?

Answer 6

• Bronchoconstriction (M₃)

Question 7

What are the effects of sympathetic stimulation on the GI tract?

Answer 7

• Smooth muscle: ↓ Motility (α, β₁)
• Sphincters: Constriction (α, β₁)
• Glands: No effects [↓ secretion (α₂)]

Question 8

What are the effects of parasympathetic stimulation on the GI tract?

Answer 8

• Smooth muscle: ↑ Motility, ↑ tone (M₃, M₂ respective)
• Sphincters: Dilation (M₃)
• Glands: Secretion & ↑ acid secretion (M₃, M₁ respective)

Question 9

What are the effects of sympathetic stimulation on the skin?

Answer 9

• Sweat glands: Secretion (via M₃ cholinergic receptors and ACh released from post-ganglionic neurone)
• Pilomotor muscles: Contraction (α)

Question 10

What are the effects of sympathetic stimulation on the eyes?

Answer 10

• Dilator pupillae muscles: Contraction and pupil dilation (mydriasis) (α₁)
• Ciliary muscles: Relaxtion (β₂)
• Lacrimal glands: ↑ Secretion (α)

Question 11

What are the effects of parasympathetic stimulation on the eyes?

Answer 11

• Constrictor pupillae: Contraction and pupil constriction (myosis) (M₃, M₂)
• Ciliary muscles: Contraction (M₃, M₂)
• Lacrimal glands: ↑ Secretion (M₃, M₂)

Question 12

What are the effects of sympathetic stimulation on the bladder?

Answer 12

• Detrusor muscle: Relaxation (β₂)
• Sphincter: Contraction (α₁)

Question 13

What are the effects of parasympthetic stimulation on the bladder?

Answer 13

• Detrusor muscle: Contraction (M₃ > M₂)
• Sphincter: Relaxation (M₃ > M₂)

Question 14

What are the effects of sympathetic stimulation on the kidneys?

Answer 14

↑ Renin secretion (β₁)

Question 15

What are the effects of sympathetic stimulation on the liver?

Answer 15

• Glycogenolysis
• Gluconeogenesis (α, β₂)

Question 16

How can parasympathetic stimulation cause vasodilation?

Answer 16

Stimulating endothelium to release NO

Question 17

Where are non-peptide neurotransmitters synthesised in pre-synaptic neurone?

Answer 17

Pre-synaptic terminal

Question 18

What is the process by which NT enzymes are transported to nerve terminal?

Answer 18

Slow axonal transport

Question 19

What is the process by which clear-cored vesicles are transported to the nerve terminal?

Answer 19

Fast axonal transport (ATP-dependent)

Question 20

What is the process by which neuropeptide vesicles are transported to the nerve terminal?

Answer 20

Fast axonal transport (ATP-dependent)

Question 21

Which protein is fast axonal transport dependent on?

Answer 21

Kinesin

Question 22

What is the process by which vesicles are transported back to the cell body from nerve terminal?

Answer 22

Retrograde axonal transport (ATP-dependent)

Question 23

Which protein is retrograde axonal transport mediated by?

Answer 23

Dyenin

Question 24

What types of NT are stored in small clear-cored vesicles?

Answer 24

Non-peptide NTs

Question 25

What type of NT is stored in large dense-cored vesicles?

Answer 25

Neuropeptides

Question 26

What diseases affect pre-synaptic terminal?

Answer 26

• Congenital myasthenic syndromes: Inadequate number of vesicles as a result of defect in synthesis/recycling.
• Familial infantile myasthenia: May be caused by a decrease in number and diameter of vesicles. May be due to impaired vesicle recycling/production.
• Lambert-Eaton Myasthenic Syndrome: Caused by autoimmune attack of pre-synaptic N-type CaVs.

Question 27

What is the structure of the core trans-SNARE complex?

Answer 27

• 4 α-helices:
  1. 2 from SNAP-25
  2. 1 from synaptobrevin
  3. 1 from syntaxin

Question 28

What is the structure of synaptotagmin?

Answer 28

• N-terminus embedded into vesicular membrane.
• C-terminus has 2 C2 domains (C2A, C2B) that bind to Ca²⁺ with low affinity, so high [Ca²⁺] needed.

Question 29

What are the functions of synapsins?

Answer 29

• Binds to vesicles when non-phosphorylated but dissociated after Ca²⁺-dependent phosphorylation.
• Dissociation allows vesicles to dock with pre-synaptic membrane.

Question 30

What are the toxins that inhibit NT release?

Answer 30

• Botulinum toxin: Causes muscle weakness due to inhibition of NMJ activity.
• Tetanus toxin: Causes muscle spasms due to inhibition of central inhibitory synapses.

Question 31

What are the toxins that stimulate uncontrolled release of NT?

Answer 31

• α-Latrotoxin: Causes uncontrolled release of ACh at NMJ, resulting in NT depletion and subsequent paralysis. May be mediated by formation of Ca²⁺ pores.

Question 32

What are the targets of botulinum toxin?

Answer 32

• A, E: SNAP-25
• B, D, F, G: Synaptobrevin

Question 33

What is the target of tetanus toxin?

Answer 33

Synaptobrevin

Question 34

What are the possible targets of α-latrotoxin?

Answer 34

• Neurexin 1
• Calcium-independent receptor of α-latrotoxin 1 (CICL1)

Question 35

What are the different types of vesicles found in pre-synaptic terminal?

Answer 35

• Clear-cored vesicles: Contains NT
• Dense-cored vesicles: Contains neuromodulators