Lecture 3 - ANS - The ganglion and adrenergic synaptic transmission

Question 1

What is the CNS made up of?

Answer 1

Brain and spinal cord

Question 2

What nerves is the peripheral nervous system made up of and what does it do?

Answer 2

Cranial Nerves (12 pairs of cranial nerves)
Spinal Nerves (31 pairs of spinal nerves)

Convey signals between the CNS and the tissues

Question 3

Role of the ANS

Answer 3

Subconscious control of organs and homeostasis
Controls all outputs from CNS to the body except somatic motor innervation (to skeletal muscle)

Question 4

What does the ANS do in cardiovascular regulation?

Answer 4

Control of HR
Contraction and relaxation of smooth muscle in blood vessels and organs
Regulation of glandular secretion
Metabolism

Question 5

Name the two neurones in the two neutron system

Answer 5

Pre and post ganglionic

Question 6

Describe the preganglionic neuron

Answer 6

Cell body is in the CNS
Small diameter and myelinated
Synapses at the autonomic ganglia
Preganglionic fibre releases Ach
Ace acts on nicotinic receptors on the post synaptic neuron

Question 7

Describe the postganglionic neuron

Answer 7

Cell body in autonomic ganglion
Small diameter, unmyelinated
Synapses close to target organ

Question 8

Describe the autonomic ganglion

Answer 8

Interface between the pre and post-ganglionic neurones of the autonomic nervous system in both sympathetic and parasympathetic branches

Question 9

What are the physiological consequences of ganglionic nicotinic receptor stimulation?

Answer 9

Sympathetic and parasympathetic post-synaptic nerve activation
Secretion of adrenaline from the adrenal medulla
Sympathetic responses dominate

Stimulation of all peripheral ganglia:
Tachycardia
Increased in BP
Increased secretions
Increased adrenaline into the blood

Question 10

Name ganglionic blocking drugs

Answer 10

Hexamethonium - non depolarising nicotinic antagonist - no clinical uses - historically used as an hypertensive
Local anaesthetics - sympathetic ganglion block - blocks sympathetically mediated pain pathways

Question 11

How are transmitters synthesised

Answer 11

Postganglionic fibres send axons to target organs
Enzymes involved in transmitter synthesis are made in the cell body
Synthetic enzymes transported to nerve terminals
Transmitter made at terminal varicosities

Question 12

What do most postsynaptic fibres release?

Answer 12

Noradrenaline

Question 13

How is noradrenaline synthesised?

Answer 13

Initial stages of synthesis in the cytoplasm
Final stages of synthesis on the membrane of synaptic vesicle
Precursor molecules are the amino acid L-tyrosine
Final Product NA - regulates synthesis via negative feedback process on initial step of synthesis

Question 14

Describe how guanethidine inhibits release of NA

Answer 14

Substrate for NET and VMAT - accumulates in vesicles, stabilises vesicles, displaces NA (slowly), free NA metabolised by MAO
High doses - destroys neuron
Overal effect - block of adrenergic neurones
Used as a antihypertensive

Question 15

Describe how Reserpine inhibits release of NA

Answer 15

Inhibits VMAT, prevents transport of NA into vesicles, cytoplasmic NA metabolised by MAO, Vesicular levels fall
Used as a antihypertensive

Question 16

What are the unwanted effects of inhibiting NA synthesis/release?

Answer 16

General all agents cause anti-sympathetic effects:
- hypotension
- bradycardia
- digestive disorders
- nasal congestion
- sexual dysfunction

Central effects common
sedation
mood disturbances

Question 17

Describe how methylodopa inhibits release of NA

Answer 17

Metabolised to methyl NA (false precursor molecules) - peripheral and central effects on BP
Inhibits DOPA decarboxylase
Used in the treatment of high BP, especially in pregnancy

Question 18

How is NA metabolised?

Answer 18

NA metabolised by either:
Monoamine oxidase (MAO) - found in neurones, also liver and GI tract
NA => DOMA

Catechol-o-methyl transferase
- neuronal and non-neuronal tissue
- also metabolises DOMA produced from MAO
- Liver COMT metabolites circulating catecholamines

Question 19

What is the initial enzyme involved in the formation of NA? and what inhibits it?

Answer 19

Tyrosine hydroxylase
Inhibits by a alpha-methyl-p-tyrosine

Question 20

Symptoms of a catecholamine-secreting tumour

Answer 20

Headaches
Heavy sweating
Rapid heartbeat (tachycardia)
High blood pressure
Pale Face
Feeling or being sick
Feeling anxious or panicky shakiness (tremor)