Functions of autonomous
nervous system
No conscious control – involuntary nervous system
- Homeostasis
- Alters intrinsic activity of tissues, e.g.
Regulation of - body temperature
- cardiovascular activity
- respiratory functions
- digestive functions
Division and functions of the ANS
1) Sympathetic Nervous System
Flight or Fight –anxiety and attention
2) Parasympathetic Nervous System
Rest and digest – relaxation and pleasure (chillin’)
ANS is organized in ganglions,
nerves and plexuses.
ANS control by CNS
Brainstem and hypothalamus (via medulla)
- control centers for:
– body temperature (H., medulla)
– water balance (H.)
– food intake (H.)
– vasomotor control of blood pressure (H., medulla)
– respiratory center (brainstem)
- Input to ANS control centers:
1) Periphery (chemoreceptors, baroreceptors)
2) Cortex-thalamus-hypothalamus
Hypothalamus
Sympathetic autonomic center:
Control of heart rate, BP via medulla
look at picture
Visceral organs
2 motor neurons:
1. Preganglionic neuron
2. Postganglionic neuron
Skeletal muscle
1 somatic motor neuron
“Generic” neurotransmitter mechanism
- an action potential is spread to the terminal of a presynaptic neuron
- Ca2+ enters the presynaptic axon terminal
- neurotransmitter is released by exocytosis into the synaptic cleft
- neurotransmitter binds to receptor sites on the postsynaptic neuron
- specific ion channels open up in the subsynaptic membrane
Cholinergic receptors
Nicotinic AChR (N)
- cation channel normally closed
- when agonist binds it opens
- influx of sodium and calcium = depolarising the cell and activates it
- in muscle if activated = contractions
- if a neuron is activated = release of other neurotransmitters
Muscarinic AChR (M)
- The even receptors m2 and m4 are inhibitory receptors and they work by activating a … and inhibitory protein and that then blocks the activity of adenelate cyclase.
So less camp production.
With less camp our heart rate increases
Parasympathetic nervous system
rest and digest
Eyes: pupil constriction
Heart: decreased heart rate
(negative chronotropy and no
significant inotropic effects)
Arteries and veins (indirect): decreased blood pressure & redistribution of blood flow toward GI tract
Stomach and intestines:
increased motility and secretions to promote digestion
Relaxation of sphincters
Liver: decreased glycogenolysis
Lungs: constriction of trachea
& bronchi
How to memorise effects of muscarine
(parasympathetic innervation)?
DUMBELS
Diarrhea/diaphoresis
Urination
Miosis
BBB (Bronchorrhea Bronchospasm Bradycardia)
Emesis
Lacrimation
Salivation
All effects elicited by the parasympathetic NS in the
end organs are though muscarinic effects!
Sympathetic nervous system: adrenergic receptors
Eyes: M. pupil dilation
Heart: increased heart rate & force of beating (positive chronotropy and inotropy)
Lungs: relaxation of trachea & bronchi to facilitate respiration
Liver: increased glycogenolysis
Adrenals: NA and A release
Stomach & GI: decreased motility
sphincter constriction
α2 is mainly presynaptic and inhibits NA release
Sympathetic Nerves
- Originate in thoracic-lumbar sections of spinal cord
- Synapse in paravertebral ganglia or prevertebral ganglia or in adrenal medulla
- Pre-ganglionic neurons release acetylcholine onto nACHR on the post-ganglionic neurons
- Post-ganglionic neurons release noradrenaline onto various adrenergic receptors on the end organs
Exception:
release of ACh by postganglionic fibers: sweat glands
Catecholamines:
Tyrosine-derived neurotransmitters
Tyrosine
DOPA
dopamine
Noradrenaline (Norepinephrine)
Adrenaline (Epinephrine)
Adrenal Medulla
- Preganglionic fibers from the hypothalamus pass through
the sympathetic ganglionic chain without synapsing into the
adrenal medulla. - They synapse directly onto chromaffin cells, modified neurons,
which release noradrenaline (NA) and adrenaline (A) into the blood. - The action of NA and A in blood are longer lasting than if the hormones were released at synapses. The hormones can reach organs that are not innervated by the ANS, such as
the lung.
Pupillary muscles and their response
constrictor: sphincter
Parasympathetic NS; Miosis
Muscarinic ACh rec
dilator: radial
Sympathetic NS; Mydriasis
Alpha1 adrenergic rec
Transmitters and Receptors in the ANS
Noradrenaline / Adrenaline =
Adrenergic receptors GPCR
- α (α1, α2)
- β (β1, β2)
Acetylcholine =
Nicotinic ACh receptors
- cation channel
Muscarinic ACh receptors
- M1-M5 GPCR
Muscarinic Ach receptors are
1000x more sensitive to Ach
than nicotinic receptors
Muscarinic acetylcholine receptors
M1 M3 M5
= IP3/DAG
CNS, glands,
smooth muscle, GIT
M2 M4
=cAMP
Heart , CNS:
K + conductance ↑
Ca2+ conductance ↓
Pharmacology of drugs targeting
the muscarinic receptors
Muscarinic agonists:
e.g. carbachol (experimental), pilocarpine
Muscarinic antagonists:
- atropine, scopolamine
What are the effects and side effects?
What would be an antidote to Atropine?
Uses of muscarinic agonists
Pilocarpine:
Treatment of glaucoma, dry mouth
Side effects/poisoning:
muscarinic side effects and seizures!
How do we treat poisoning?
Atropine or a muscarinic antagonist.
Regulation of aqueous humor pressure
Muscarinic rec. increase aqueous
humor outflow by constriction of
ciliary muscle and pupil constriction
Treatment of glaucoma: enhance
muscarinic activity (pilocarpine,
ACHEI) or beta-blockers
Beta2 adrenergic rec. mediate aqueous humor production
Muscarinic antagonist effects
Atropine:
- mydriasis, blurred vision
- Tachycardia (80-90 bpm)
- Bronchodilation
- Dry mouth and skin (no sweating)
- Urinary retention
- Constipation
CNS: excitement, hyperactivity, rise in body temperature
Scopolamine: sedation, hallucinations, anti-emetic
Uses of muscarinic antagonists
Atropine and derivatives:
- To induce mydriasis (ophtalmologist - homatropine)
- Asthma (ipratropium)
- During surgery: to inhibit vagal reflexes
(Inhibit bronchoconstriction + bradycardia)
Hyoscine (scopolamine) patch:
- To prevent motion sickness
Drugs changing cholinergic transmission
Botulinum toxin A: Clostridium botulinum = strongest known poison!
0.1-1 ng/kg lethal dose
(100 g can kill mankind)
-Treatment for wrinkles and
dystonia, strabismus,
spasticity
-Inhibition of exocytosis
proteins and block of release
of ACh (and other NTs)->
Flaccid paralysis of muscles
Acetylcholinesterase inhibitors:
(indirect parasympthomimetic
agents):
Irreversible: Insecticides
Organophosphates
(soman, sarin)
Enhanced ACH neurotransmission
(Nicotinic +) Muscarinic
(DUMBBBELS)
Skeletal muscle, Postganglionic cell or
effector organ innervated by
parasympathetic NS
Acetylcholinesterase inhibitors
“Agonistic” effects on
neuromuscular junction:
greater muscle tension
Treatment of myasthenia
gravis
“Agonistic” effects on
muscarinic synapses:
Treatment of glaucoma, GIT
immobility
Effect on CNS:
Treatment for Alzheimer’s
Disease (e.g. donezepil)
