4.1 Introduction to the autonomic nervous system

Question 1

The autonomic nervous system is divided into sympathetic and parasympathetic systems:
• Sympathetic system primarily takes care of the fight-or-flight response while the parasympathetic system takes care of the rest-and-digest response
• Many tissues receive innervation from both systems → tend to be of opposite effects
• Some organs (e.g. ___________________________) predominantly receive sympathetic input → may dilate or constrict blood vessels
o Differences in effect is mediated by the receptors (not the nerves)

• Salivary glands receive both sympathetic and parasympathetic inputs of similar effects (__________________), but the parasympathetic input is more important in terms of digestive function while the sympathetic input is for immune function
• Gut possesses its own nervous system (enteric nervous system) → local nervous control over GI function (independent from CNS influence)
o Responds to environmental changes within the gut (e.g. motility, blood flow, lumen environment)

Answer 1

liver, adipose, kidneys, blood vessels;

increased saliva production

Question 2

effect of sympathetic on eye

Answer 2

dilation (pupil)

Question 3

effect of parasympathetic on eye

Answer 3

constriction (pupil), contraction (ciliary muscle)

Question 4

effect of sympathetic on trachea and bronchioles

Answer 4

dilates

Question 5

effect of parasympathetic on trachea and bronchioles

Answer 5

constriction

Question 6

effect of sympathetic on liver

Answer 6

gluocgenolysis, glucogenesis

Question 7

effect of sympathetic on adipose

Answer 7

lipolysis

Question 8

effect of sympathetic on kidney

Answer 8

increased renin secretion

Question 9

effect of sympathetic on ureters & bladder

Answer 9

relaxes detrusor, constricts trigone & sphincter

Question 10

effect of parasympathetic on ureters & bladder

Answer 10

relaxes detrusor, relaxes trigone and sphincter

Question 11

effect of sympathetic on salivary glands

Answer 11

thick, viscious secretion

Question 12

effect of parasympathetic on salivary glands

Answer 12

watery copious secretion

Question 13

effect of sympathetic on skin

Answer 13

piloerection, increased sweating

Question 14

effect of sympathetic on heart

Answer 14

increase rate & contractility

Question 15

effect of parasympathetic on heart

Answer 15

decrease rate & contractility

Question 16

effect of sympathetic on gi

Answer 16

decrease motility and tone; sphincter contraction

Question 17

effect of parasympathetic on gi

Answer 17

increase motility and tone, increase secretions

Question 18

effect of sympathetic on blood vessels (skeletal muscle)

Answer 18

dilatation

Question 19

effect of sympathetic on blood vessels (skin, mucuous membranes and splanchnic area)

Answer 19

constriction

Question 20

There are two different types of acetylcholine receptors – nicotinic and muscarinic:
• Parasympathetic effects predominate at rest → blocking nicotinic receptors leads to an ________________ at rest
• Sympathetic effects predominate during exercise → blocking nicotinic receptors leads to a _______________ during exercise (hypothetical)

Nicotinic receptors

• Found in all _________________ (allows for propagation of signals onto the postganglionic neurone)
• Interference affects all autonomic functions

Muscarinic receptors

• Found within the ______________ (mediates parasympathetic effects)
• Interference affects only __________________

Answer 20

increase in heart rate;

decrease in heart rate;

autonomic ganglia;

effector tissues;

parasympathetic response

Question 21

Nicotinic acetylcholine receptors (nAChR) are found in both sympathetic and parasympathetic ganglia, stimulated by _____________ and inhibited by _______________:
• ________________ receptor → acetylcholine binding causes ion channel opening, ion influx and excitation of postganglionic neurone
• Rapid response (_________ for whole process from release of ACh to signal propagation)

Answer 21

ACh and nicotine;

hexamethonium;

Type I (ionotropic);

few ms

Question 22

what are the AchR subunit in muscle type (in skeletal muscles)

Answer 22

2 α, β, δ, ε

Question 23

what are the AchR subunit in ganglion type (in CNS )

Answer 23

2 α, 3 β

Question 24

why is there bronchodilation when nicotinic receptors in resting individuals are blocked?

Answer 24

Parasympathetic nervous system normally keeps the bronchi partially constricted (if not they will start to dilate)

Question 25

why is there decreased sweat production when nicotinic receptors in resting individuals are blocked?

Answer 25

nAChR are involved in sweat production

Question 26

why is there constipation when nicotinic receptors in resting individuals are blocked?

Answer 26

Parasympathetic system increases gut motility (blocking its effects causes the gut to slow down)

Question 27

why is there decreased urinary frequency when nicotinic receptors in resting individuals are blocked?

Answer 27

Parasympathetic system contracts the bladder detrusor smooth muscle and relaxes the urethral sphincter (urinary frequency decreases and retention occurs if blocked)

Question 28

why is there longsightedness when nicotinic receptors in resting individuals are blocked?

Answer 28

Parasympathetic system innervates the ciliary muscle (via CN III through ciliary ganglion) → allows it to contract to focus on near objects (i.e. acutely promotes short-sightedness): • Lens becomes more spherical → focal length decreases • Ciliaris paralysed if blocked → cannot focus near objects

Question 29

Muscarinic receptors are found in all effector organs receiving _________________ and tissues receiving __________________: • Stimulated by muscarine and ACh (actions correspond to parasympathetic effects) and inhibited by atropine (after atropine blockage of muscarinic actions, larger ACh doses can induce effects similar to those caused by nicotine) • ___________________ receptor → ACh binding promotes G-protein activation and generation of second messenger which activates cell signalling pathways • Fast response (_______________; slower than Type I receptors) *M1, M3, M5 work via ________________ (influences intracellular Ca2+), while M2 and M4 work via _______________.

Answer 29

postganglionic parasympathetic fibres; postganglionic sympathetic cholinergic fibres; Type II (G-protein coupled); seconds to minutes; Gq stimulation of IP3 and DAG; Gi reduction of cAMP

Question 30

what are the functions of M1 receptors?

Answer 30

gastric parietal cells, salivary glands

Question 31

What are the functions of M2 receptors?

Answer 31

cardiac cells and smooth muscles

Question 32

What are the functions of M3 receptors?

Answer 32

bladder, exocrine glands (sweat, salivary), smooth muscles, eyes

Question 33

What are the functions of M4 receptors?

Answer 33

regulate striatal DA release, modulate PPI, analgesia, keratinocyte migration

Question 34

What are the functions of M5 receptors

Answer 34

cerebral arterial vasoconstriction

Question 35

ADRENERGIC RECEPTORS Adrenoceptors are found at all effector organs innervated by postganglionic sympathetic fibres (except organs like sweat glands), stimulated by noradrenaline (NA) and adrenaline: *α1-adrenoceptors work via _________________ while α2 and β adrenoceptors work via _______________ respectively (increased intracellular cAMP is stimulatory on the heart, and inhibitory in vascular smooth muscles and platelets) • _____________ receptors → similar mechanism to muscarinic receptors • 4 main subtypes (α1, α2, β1, β2) with different effects and locations in the body o Mnemonic: AC-BD (alpha-constrict; beta-dilate), 1 heart, 2 lungs

Answer 35

Type II (G-protein coupled); Gq stimulation of IP3 and DAG (increases intracellular Ca2+); Gi and Gs effects on cAMP

Question 36

what are the functions of α1 receptors?

Answer 36

Mainly on effector cells (e.g. smooth muscles) (causes contraction)

Question 37

what are the functions of α2 receptors?

Answer 37

Mainly on presynaptic membranes (causes inhibition of NA release → negative feedback); some on smooth muscles of certain blood vessels (vasoconstriction)

Question 38

what are the functions of β1 receptors?

Answer 38

Mainly in the heart (causes increased contractility and heart rate)

Question 39

what are the functions of β2receptors?

Answer 39

Mainly in the lungs/bronchi (causes bronchodilation)

Question 40

The synthesis, release, metabolism of amine transmitters (e.g. ACh) follow the same steps: 1. Precursor molecule (acetyl-CoA and choline) is converted into the transmitter (ACh) 2. Neurotransmitters are packaged into vesicles sitting near the cell surface membrane 3. Wave of depolarisation promotes ____________, driving exocytosis of synaptic vesicles to release the neurotransmitters into the synaptic cleft 4. Neurotransmitter molecules diffuse across the synaptic cleft 5. Binding to receptors on the postsynaptic membrane 6. Synaptic transmission is terminated via __________________ 7. Neurotransmitter molecules or breakdown products are removed from the synaptic cleft via uptake mechanisms into the presynaptic membrane

Answer 40

Ca2+ influx; enzymatic metabolism (acetylcholinesterase breaking ACh back down into acetate and choline)

Question 41

Noradrenaline is produced from the precursor tyrosine taken up into the neurone, via 3 enzyme-catalysed steps (first conversion is rate-limiting): 1. Tyrosine → DOPA (via ____________); DOPA → dopamine (via ____________); dopamine → NA (via _____________ packaged in the same vesicle) 2. Same process as ACh then occurs, with the release of NA to activate postsynaptic adrenoceptors 3. No enzymatic breakdown of NA within the synapse occurs (removed from the synapse via uptake proteins)

Answer 41

tyrosine hydroxylase; DOPA decarboxylase; dopamine β hydroxylase

Question 42

how is NA being uptaked?

Answer 42

- Uptake of NA back into the presynaptic neurone → broken down by monoamine oxidase A (MAO-A) - Uptake of NA into other tissues (e.g. postsynaptic cell) → broken down by catechol-O-methyltransferase (COMT)