Autonomic Pharmacology I

Question 1

Nervous system and subdivisions?

Answer 1

Nervous system can be divided into:
CNS (brain and spinal cord)

PNS:
Somatic NS
Somatic efferent supply skeletal muscle, for example
Somatic and visceral afferent

Enteric (ENS) - part of ANS but is within walls of GI tract, allowing regulation of gut function (largely independent of rest of NS)

Autonomic (ANS) - sympathetic and parasympathetic division

Question 2

Difference between afferent and efferent?

Answer 2

Afferent - towards CNS

Efferent - away from CNS

Question 3

Over all functions of the ANS?

Answer 3

Responsible for carrying output from CNS to whole body, with EXCEPTION of skeletal muscle

Regulates visceral functions that are largely INVOLUNTARY, e.g:
Contraction/relaxation of vascular and visceral smooth muscle
All exocrine and certain endocrine secretions
Heartbeat
Aspects of metabolism, part. liver and skeletal muscle)

Question 4

Control of ANS?

Answer 4

Training allows a degree of control of some ANS functions, e.g: urination, defecation

Question 5

Sympathetic and parasympathetic subdivisions of ANS?

Answer 5

Often work in an opposing fashion to maintain homeostasis
Parasympathetic ANS - coordinates body’s basic homeostatic functions, sedentary and “rest and digest”

Sympathetic ANS - coordinates body’s response to stress, associated with fight/flight reactions

Question 6

What is a ganglion?

Answer 6

Collection of nerve cell bodies in the PNS; CNS equivalent is a nucleus

Question 7

Transmitters in sympathetic division?

Answer 7

Preganglionic neurones (cholinergic) - acetylcholine (ACh)

Postganglionic neurones (usually adrenergic) - noradrenaline

Question 8

Transmitters in parasympathetic division?

Answer 8

Preganglionic neurones (cholinergic) - acetylcholine

Postganglionic neurones (cholinergic) - acetycholine

Question 9

Describe the sympathetic outflow

Answer 9

Sympathetic nerves in lateral horns of spinal cord (T1-L2) - AKA thoracolumbar outflow

Question 10

Describe the parasympathetic outflow

Answer 10

Cranial nerves 3, 7, 9 and 10

Cranio-sacral outflow

Question 11

Where do pre- and post-ganglionic neurones synapse?

Answer 11

Prevertebral ganglia

Paravertebral ganglia

Question 12

Where are parasympathetic ganglia normally?

Answer 12

In target organs, e.g: discrete ganglia in head and neck

Question 13

Effect of ANS on organs?

Answer 13

Sympathetic stimulation:
Increases HR
Increases force of contraction

Relaxes bronchi (via release of adrenaline)
Decreases mucous production (decreases airway resistance)

Reduces motility
Constricts sphincters

Constricts in most location but relaxes in skeletal muscle

Release of adrenaline from adrenal glands

Ejaculation

Parasympathetic stimulation:
Decreases HR

Constricts bronchi
Stimulates mucous production (increases airway resistance)

Increases motility
Relaxes sphincters

Largely no effect

No effect on adrenal gland

Erection

Question 14

How does neurochemical transmission occur?

Answer 14

1. Uptake of transmitter precursor into neuron
2. Synthesis of transmitter
3. Storage of transmitter in vesicle
4. DEPOLARISATION by action potential
5. Ca2+ INFLUX through voltage-activated Ca2+ channels
6. Ca2+ binds to the vesicle causing Ca2+ induced release of transmitter (exocytosis)
7. Receptor activation
8. Enzyme-mediated inactivation of transmitter
   OR
   Re-uptake of transmitter

Question 15

Fates of different neurotransmitters?

Answer 15

Acetylcholine - enzyme-mediated degradation

Noradrenaline - re-uptake of transmitter in pre-synaptic cell or in non-neurone cell

Question 16

Describe chemical transmission in the sympathetic division of the ANS

Answer 16

Action potential originating in the CNS:
Travels to pre-synpatic terminal of the preganglionic neurone triggering Ca2+ entry and the release of ACh

ACh open LIGAND-GATED ION CHANNELS (NICOTINIC ACh receptors) in the postganglionic neurone, causing depolarisation and action potential generation, which travel to presynaptic terminal of neurone, triggering Ca2+ entry and the release of NORADRENALINE

Noradrenaline activates G-protein coupled ADRENOCEPTORS in the target cell membrane to cause a CELLULAR RESPONSE

Question 17

Describe chemical transmission in the parasympathetic division of the ANS

Answer 17

Process is identical to that for the sympathetic division, with exceptions:
ACh is always the transmitter used by postganglionic neurones
ACh activates G-protein coupled MUSCARINIC ACETYLCHOLINE receptors in the target cell membrane, to cause a cellular response

Question 18

Structure of ligand-gated ion channels?

Answer 18

Consist of separate glycoprotein subunits that form a central, ion conducting channel
There are transmitter binding sites between the subunits

Question 19

Function of ligand-gated ion channels?

Answer 19

Allows rapid changes in the permeability of the membrane to certain ions
Rapidly alter membrane potential

Question 20

How do ligand-gated ion channels work?

Answer 20

Agonist binds
Channel opens
Ion flow

Question 21

Describe G-protein coupled receptors

Answer 21

E.g: Muscarinic ACh receptors

Receptor, G-protein and effector are separate proteins
G-protein couples receptor activation to effector modulation

Signalling via G-proteins is slow in comparison to ligand-gated ion channels

Question 22

Structure of G-protein coupled receptors?

Answer 22

Integral membrane protein
Single polypeptide with extracellular NH2 and intracellular COOH termini

Contain 7 transmembrane proteins joined by 3 extracellular and 3 intracellular CONNECTING LOOPS

Question 23

Structure of G-proteins?

Answer 23

AKA Guanine nucleotide binding protein)

Peripheral membrane protein

Consists of 3 polypeptide subunits (α, β and γ)

Contains a guanine nucleotide binding site in the α-subunit that can hold guanosine triphosphate (GTP) or guanosine diphosphate (GDP)

Question 24

Describe G-protein coupled receptors when there is no signalling

Answer 24

Receptor is unoccupied
G-protein α-subunit binds GDP
Effector is not modulated

Question 25

Describe G-protein coupled receptors when the signal is being turned on

Answer 25

Agonist activates the receptor and G-protein couples with this
GDP dissociates from the α-subunit and GTP binds to it
G-protein dissociates into separate α, β and γ subunits
G-protein α-subunit combines with, and modifies, the activity of the effector

Agonist may dissociate from the receptor but the signal can persis

Question 26

Describe G-protein coupled receptors when the signal being turned off

Answer 26

α-subunit acts as an ENZYME (a GTPase) to hydrolyse GTP to GDP and Pi.

Signal is turned off

G-protein α-subunit recombines with the βγ-subunit, completing the “G-protein cycle”