The Autonomic Nervous System Flashcards
Which physiological functions are controlled by the Autonomic nervous system?
- Heart rate
- Blood pressure
- Airway diameter
- Eye focusing
- Secretions (e.g. saliva, sweat, mucus, enzymes)
- Bladder, Genitalia, alimentary tract action
Name some parasympathomimetric drugs
- Neostigmine
- Physotigmine
- Edrophonium
- Parathion
How do Parasympathetic postganglions produce physiological responses?
Ach released on muscarinic receptors on organs
Describe the ganglionic structure of the parasympathetic nervous system
Ach receptor –> Ach receptor
Long preganglion , shorter post ganglionic
What are cholinoceptors?
Nicotinic Ach Receptors are ligand gated ion channels that allow ions to enter
Which type of Ach receptor is present on post synaptic neuron?
Nicotinic Ach receptor
What is the effect of the vagus nerve on secretory cells?
Ach from Vagus nerve augments acid production on M1
causing secretions in salivary and sweat glands via M3
–> under sympathetic control (Adrenal gland)
What type of nAchR are there ?
Neuronal nicotinic receptors
- work on autonomic ganglion
Muscle nicotinic Receptors
- Act on skeletal muscle
Where in the body does the parasympathetic nerves act upon?
- Salivary gland
- GI Tract
- Heart
- Acid cells
What are the parasympathetic effects on the eye?
M3 contraction of circular muscle
Causes narrowing of pupils
What are NANC nerves?
Parasympathetic nerves that don’t utilise NA or Ach
Called non adrenergic non cholinergic NANC Nerves
Where in the body does the sympathetic nervous system operate?
- Arteries, heart
- Sweat glands
- Adrenal glands
What are the 2 types of cholinoceptors?
N₁/Nm - skeletal muscle
N₂/Nn - autonomic ganglia CNS
What is the effect of M3 receptors when activated?
M3 releases messengers and NO when activated
Non vascular smooth muscle contracts when M3 activated
Describe the ganglionic structure of the sympathetic nerves
Ach –> NA
Short pre ganglion , longer post ganglion
Ach –> Ach
Short pre ganglion , longer post ganglion
Ach lightly myelinated
slightly longer pre ganglion
Which neurotransmitter do most postganglionic parasympathetic neurons release?
Acetylcholine
What are the 2 neurones making up the autonomic system?
Parasympathetic
Sympathetic
Both have opposing effects on tissue (some tissues only have single nerve supply)
What are the different selective nicotinic antagonists?
Tubocararine Atropine Hysocine hexamethonium Pirenzipene Ipratorium paricuronium
What type of receptors are muscarinic receptors?
All muscarinic receptors are GPCRs involved in parasympathetic responses
What is the function of the Autonomic Nervous System?
Its a connection between the CNS and the peripheral organs
How do nAchR produce effects on their target cells?
- Ach binding causes a conformational change; opening
channel pore - Influx of cations
- Produces EJP (excitatory junction potential) in target
cell - Effect terminated by unbinding of Ach
What are some clinical uses of muscarinic blockers?
- Paramedication e.g. hyoscine used before anasthesia to reduce secretions, sedation & prevent vagal effects
- Heart - block mAchR to increase AV conduction
- Opthamology - produce pupil dilation (mydriasis) for examination
- Bronchodilation in COPD
- Antispasmidic in GI Colic
- Antiche poisoning treatment
Which neurotransmitter is present in all autonomic ganglia?
Acetylcholine
Which parasympathetic nerve effects cardiac heart rate?
Vagus nerve
What is Isoprenaline?
A synthetic research tool / medications used to treat slow heart rate
What is the effect of M2 and M4 receptors?
Coupled to Gₐ receptors
Decrease adenylate cyclase activity
Decreases [cAMP]
What are the muscarinic selective agonists?
Muscarine bethanescol
Pilocarpine
Name the various parasympathetic nerves and their location
- Cranial Nerve III (oculamotor) - pupil
- Cranial Nerve VII (facial) - submaxillary, sublingual,
lacrimal glands - Cranial Nerve IX (glossopharyngeol) - parolid glands
- Cranial Nerve X (Vagus) - heart, kidney, bronchi, GI tract
to colon - Sacral Nerves - remainder of GI Tract, bladder, &
Genitalia
Name the selective nicotinic agonists
Nicotine muscarine
Bethanecol
Lobeline
Pilocarpine
Where in the body do the 2 systems produce opposite effects?
Myocardium (heart rate & force) - PS decreases, S
increases
Intestine smooth muscle motility - PS increases, S decreases
Iris smooth muscle - PS constricted, S dilated
What is the parasympathetic effect of Ɣβ subunits on the heart?
βƔ subunits cause basal slowing of the heart
1. βƔ subunits dissociate and interact with K+ channel
GIRK
2. K+ channel permanently open - membrane
hyperpolarises
3. less Ca2+ channels open - less cAMP
4. slows heart rate - less pacemaker activity
How do sympathomimetric drugs work?
By directly binding to sympathetic adrenergic receptors
or indirectly by increasing NA levels
What are the 5 types of muscarinic receptors?
M1 - CNS, Peripheral neurons, gastric parietal cells
M2 - atria, SAN, AVN
M3 - Visceral smooth muscle, secretory glands,
endothelial cells
M4 - CNS
M5 - CNS
Which neurotransmitter do most postganglionic sympathetic neurons release?
Nor Adrenaline
What is the effect of the parasympathetic vagus nerve on heart rate?
- Membrane potential hyperpolarises
- Decreases action potentials
- M2 muscarinic receptors negatively coupled to cAMP
- less Ca2+uptake in SR
- Pacemaker in SAN less effective
What are the 2 types of adrenergic receptors?
α adrenergic receptors
- NA -> Adrenaline -> Isoprenaline
β adrenergic receptors
- Isoprenaline -> Adrenaline -> NA
What are the clinical uses of nAchR blockers?
Muscle relaxants
Direct blockers : tubocurarine pancuronium, vecuronium, atacurilum
Depolarising blockers : suramethonium
What are the two sections of sympathetic nerves?
Paravertebral chain of ganglia ~25
Prevertebral ganglia near aorta
What is the major part of the autonomic sytem, cholinergic neurons work under?
Parasympathetic responses
What is the use of adrenoceptor blockers?
Slow heart rate and improve profusion by increasing NA release
e.g. Atenolol
How do parasympathomimetric drugs work?
Inhibit Achesterase
boost cholinergic transmission of parasympathetic nerve
How do sympathetic postganglions produce physiological responses?
Release NA on adrenoceptors on organs
Why does the parasympathetic nervous system have no vascular effect ?
There are no mucarinic receptors on SAN
M3 expressed on endothelial cells lining blood vessels
How do NANC transmitters operate on the postganglionic sympathetic neurone?
Use ATP on neuropeptide Y
cause vasoconstriction
What is GIRK k+ channel?
G-Protein coupled inwardly rectifying potassium channels activated via signal transduction
Why do some postganglionic sympathetic neurones release Ach?
To stimulate Muscarinic Ach receptors on tissues
Give examples of indirectly acting parasympathomimetics
Acetylcholinesterase Inhibitors: tacrine, donepzil, rivastigmine
- used in dementia
- clinically used in neuromuscular diseases
e. g. myasthesia gravis, Eaton Lambert syndrome
Where do the 2 systems produce similar effects?
In some salivary glands they both increase secretions
Describe the structure of postganglionic motor / somatic neurons
Heavily myelinated to skeletal muscle (not part of ANS)
Summarise the sympathetic nervous system
Thoracolumbar outflow
Short preganglionic fibres
NA main terminal messenger
Which receptor type are adrenoceptors?
All adrenoceptors are G Protein Coupled Receptors
Name the paraverterbral sympathetic nerves and where they’re located
- Superior Cervical ganglia - pupil, facial glands, head
circulation - Middle & Inferior ganglia - Heart and lungs
- Remaining paravertebral ganglia - Sweat glands pilomotor (hair), muscles, skin blood vessels, and skeletal muscle
What causes cation channels to open in pacemaker regions?
Funny channels allow cations into cells (via hyperpolarisation not depolarisation)
causing Voltage gated channels to open
Do effector organs receive sympathetic or parasympathetic innervations?
Many effector organs receive signals from both parasympathetic and sympathetic
nerves with the effects often being opposite of each other
Name the muscarinic selective antagonists
Atropine
Hyoscine
Pirenzipene
Ipratorium
What is a sympathomimetric drug?
A drug that mimics the stimulation of the sympathetic nerves
Where does the prevertebral ganglia function?
GI tract
How does the NANC VIP function?
Vasoactive Intestinal Peptide
causes dilation
on salivary glands and bronchial smooth muscle
Which tissues receive a single input from parasympathetic nerves only?
- Ciliary eye muscles: accommodates near vision
- Pancreas & Sensory stomach cells - increased secretions
Which autonomic nervous system do adrenergic effects work under?
The sympathetic nervous system
What is the effect of Nitric Oxide NANC ?
Nitric oxide works on parasympathetic pelvic nerves
Causing an erection
How do Somatic nevres produce physiological responses?
Release Ach onto nAchR on motor end plates
Explain the effect of M1, M3 and M5 receptors
Coupled to G₉₁₁ receptors
Activate phospholipase C enzyme
PIP₂ –> IP₃ + DAG
What are the parasympathetic effects on muscarinic receptors?
- reduces heart rate
- vasodilation
- increased saliva & gastric acid production
- increased tear formation
- visceral smooth muscle contraction
- pupil constriction
What are the different physiological effects of adrenoceptors?
α₁ - Vascular smooth muscle contraction
α₂ - Inhibits transmitter release
β₁ - Main cardiac effects
β₂ - Vascular dilation, airway relaxation
What is the effect of β₁ adrenoceptor on cardiac action potentials?
When stimulated, cardiac contractions are stronger but depolarisation action potentials are briefer
Which tissues do sympathetic nerves supply a single input to?
- Blood vessels: mainly constricted
- Sweat glands:increased secretions
Summarise the parasympathetic nervous system
Saccrocranial outflow
Long preganglionic fibres
Ach main terminal messenger
How is the α₁ adrenoceptor activated?
- Adrenaline or NA binds to α₁ receptor
- α₁ subunit on G protein activated
- Activates Phospholipase C enzyme
- -> cleaves PIP₂ –> IP₃ + DAG - IP₃ binds to its recptor on SR
- Causes release of Ca2+ from SR
How do β adrenoceptors cause their respective effects?
β adrenoceptors are coupled to Adenyl Cyclase enzyme via Gₛ α subunit
Outline how β₁ adrenoceptors cause stronger contraction force
- Adenyl Cyclase activated by NA binding to receptor
- ATP converted to cAMP
- cAMP interacts with pacemaker channel in SAN
- cAMP activates PKA
- PKA activates Ca2+ channels - influx of Ca2+
- Increased Ca2+ uptake in SR = stronger contractions
- Briefer = Ca2+ taken up faster
How do α₂ adrenoceptors cause the negative feedback of neurotransmitter release?
- Ca2+ channels activity decreased on sympathetic
nerve terminal - NA released
- Less Ca2+ channels opened - negative feedback
- reduces levels of cAMP released
What is the effect of adrenoceptors on vascular smooth muscle?
- K+ channels open –> k+ influx (hyperpolarisation)
- Cell ready for contraction again
- Cardiac stimulation increased by β₁ adrenoceptors
- β₁ & β₂ relax vascular smooth muscle (esp. airways)
What is the effect of an activated α₁ adrenoceptor?
Contraction of:
- Vascular smooth muscle
- Iris muscle (pupil dilation)
- Pilomotor muscle
Which antagonist is a parasympathomimetric drug effecting the eye?
Atropine belladonna blocks cholinergic receptors in the eye causing the pupilto open
Explain how β₂ adrenoceptors are activated
- more K+ activity (than in cardiac cells)
- less dominant release process
- Ca2+ uptake
- PKA inhibits smooth muscle contraction as
tropomyosin not phosphorylated
Outline how β adrenoceptors cause renin release in kidney
Juxta glomular apparatus (JGA) located between afferent and efferent renal
arteries => increase renin release when:
Angiotensinogen (inactive) –> Angiotensin I (active)
Name some directly acting parasympathomimetics and their functions
Pilocarpine (mAchr agonist) - treats glucoma & dry mouth, used in sweat tests
Bethanecol (mAchR agonist) - occasionally used to aid bladder/gastric emptying
Succinylcholine (nAchR agonist) - high affinity: used in surgery depolarising paralysis
What other processes are β adrenoceptors involved in?
- Carbohydrate metabolism (β₁)
- Renin release from kidney
- Lipolysis (β₃)
How is Glucoma caused?
Stems from poor drainage of fluid though trabecular network
often due to dilated iris
What is the sympathetic effects of α₁ receptors on the eye?
α₁ contraction of radial muscle
Muscarinic receptors on ciliary muscles
- pull on suspensory ligaments allowing lens to bulge
Summarise the effect of adrenoceptors on smooth muscle
Increased cAMP –> decreased Ca2+ release / increased K+ channel activity
–> decreased myosin light chain kinase –> decreased contraction
Name some uses of adrenoceptor agonists
Eye drops - ephedrine, brimonidine
Nasal decongestant - phenylephrine, ephedrine
Prolongation of local anaesthetic - adrenaline
Asthma inhalers - salbutamol (ventolin)
Cardiac stimulants - adrealine, dobutamine
Anti-obesity - BRL37344 in development
Acute anaphylaxis - adrenaline
Premature labour - β agonists
Overactive bladder - β₃ agonist mirabegron
What is parathion?
Parasympathomimetic: Highly toxic cholinesterase inhibitor
so Ach not broken down
What causes the effect of adrenoceptors on cardiac and smooth muscle to be so different?
Despite the same receptors and process, the effect is opposite due to the difference in cell type
