autonomic nervous system Flashcards
ganglion neurone
collection of neuronal bodies found in the voluntary and autonomic branches of the peripheral nervous system (PNS).
Parasympathetic paths
Cranial nerve III controls eyes
Vagus nervous system controls glands
sacral s2-s4 controls the bladder and genitals
What acetylcholine affects
Somatic- skeletal muscle
Sympathetic-glands, adrenal medulla
Parasympathetic- salivary glands
Types of receptors for acetylcholine
Muscuerinic
Nicotonic
Nicotinic acetylcholine receptor
Ligand gated channel that has 5 sub units
Has 2 binding spots for Ach
Stimulates adrenaline secretion from adrenal medulla
Muscarinic Ach receptor
G protein coupled receptor
Causes release of calcium ions and inhibits
Causes activation of sweat glands
M2 receptor(cardiac)
Decreased cAMP
Causes inhibitory affect
Potassium ion increase and calcium ion decrease
Ca2+ decreases heart rate
M1 receptor(neural)
Activates phospholipase C increasing IP3 and DAD
Excites CNS and ganglia
M3 receptor
Activates phospholipase C and increases IP3 and DAG
Causes smooth muscle contraction and vasodilation
cholinergic transmission
Acetylcholine can be taken back to the presynaptic terminal by the transporter choline carrier
Choline can then be catalysed by choline acetyltransferase to form Ach again
This can then be transported back to the vesicle through Ach carrier choline
Drugs on cholinergic transmission
Atropine inhibits the effect of acetylcholine by complexing the acetylcholine receptor
Cholinesterase inhibitors function to decrease the breakdown of acetylcholine
depolarizing agents vs nondepolarizing
depolarizing muscle relaxants act as ACh receptor agonists, whereas nondepolarizing muscle relaxants function as competitive antagonists
Muscuerinic agonists
Acts for parasympathetic system Decreased heart rate smooth muscle contraction Sweating and salvation Affects CNS by causing excitation
Nicotine
stimulates ganglia and neuromuscular junction and causes a depolarising block
Depolarising block is now desensitised to anymore depolarisation
It can cause many undesirable effects
Ganglion blockers
Block muscle contractions therefore blocking skeletal muscle BY BLOCKING OF nicotine receptors
This can be dangerous because the diaphragm needs to be able to contract so therefore we need artificial ventilation to assist breathing
Non depolarising agents
Can be long term, short term or intermediate
Eventually all the drugs will need to be metabolised in the liver and released from the kidney
If these organs are impaired then they can remain in the body longer and cause more effects
Acetylcholine in muscle cells
Muscle cells cannot be repolarised so when acetylcholine binds to the receptor they cannot cause further depolarisation causing desensitisation
Phase 2 is consistently depolarised and cannot repolarise causing muscle relaxation
Acetylcholinesterase
AChe main function is to hydrolyse acetylcholine in the blood
Causes increased skeletal muscle contraction
Has short, medium and irreversible duration
Sympathetic and parasympathetic systems
Sympathetic pathway(adrenergic) uses norepinephrine neurotransmitter and parasympathetic uses acetylcholine
Adrenaline
Adrenaline can cause vasoconstriction in vascular beds
There is alpha adrenaline receptor neuroadrenaline> adrenaline>isoproternal
adrenoreceptors
Two subtypes for alpha adrenoreceptors
Three subtypes for beta adrenoreceptors
All use G proteins
A1 adrenoreceptor
Activates phospholipase C increasing IP3 and DAG
Constriction of smooth muscle in blood vessel
A2 adrenoreceptors
mainly expressed in the presynaptic terminal
Reduces cAMP
Inhibition of neurotransmitters
Decreased insulin secretion
adrenoreceptor antagonist
Non selective can reduce blood pressure
Selective can cause hypertension
B1 adrenoreceptors
Mainly expressed in the heart
Use in heart failure which is when heart activity is reduced
Increases cAMP
Increases heart rate and contraction
B2 adrenoreceptors
Increases cAMP
Relaxes smooth muscle in bronchi
B3 andrenoreceptor
Exercise’s are mediated by B3 receptors
Increased cAMP
B3 have many clinical usage
renin is a Chemical substance produced in the kidney and activated during exercise
Can be used to correct irregular heart contraction and chest pain
B adrenoreceptor antagonist
Decrease blood pressure and sympathetic output
B adrenoreceptor causes reduction of heart rate and reduces bronchoconstriction
Selectivity in drugs
Ideal drug will be selective to a certain subtype
beta 1 adrenoreceptor specific to slow heart rate
Drugs are selective not specific
Adrenergic neurotransmission
Processes in the synapse of somatic nerve terminal
Localised effect on vasoconstriction)Noradrenaline
CA has 3 neurotransmitters that is secreted at adrenal medulla into the blood and cause a widespread effect
CA
Adrenaline, noradrenaline and dopamine secreted as a hormone to cause widespread effect
synthesis of CA
Synthesis of CA uses multiple enzymes to catalyse the reaction
First enzyme adds an hydroxyl group
Next enzyme removes of carboxyl group
Next enzyme adds a hydroxyl group on to form noradrenaline
PNMT adds another carboxyl group
The first enzyme called Tyrosine hydroxlase is red limiting step and is critical for all production of adrenaline
Dopamine in CA
Dopamine is transported into the vesicle of nerve terminal by transporter
Once in the vesicle it can form noradrenaline due to the presence of DBH enzyme
Noradrenaline in CA
Noradrenaline is released via exocytosis calcium is required.
Noradrenaline is released onto post synaptic adrenoreceptors
Indirectly acting sympathomimetic amine promotes the release of noradrenaline
Once noradrenaline is released into the synaptic cleft there can be re uptake and go back into the vesicle again
CA stages
synthesis storage release interaction of adrenoreceptors on target organ and glands Degradation or re-uptake
Reuptake of noradrenaline in CA
Uptake occurs in the nerve terminals and is transported into the vesicles via VMAT’s
Dales principle(outdated)
a given neuron contains and releases only one neurotransmitter and exerts the same functional effects at all of its termination sites.
co transmission
Neurotransmission usually uses co transmission
We know that released neurotransmitters can also act on presynaptic neurones causing pre synaptic modulation
Neurotransmitter release can also vary during development and injury
Neuromodulation
It is difficult to differentiate from neurotransmissions and neuromodulation
Neuromodulation is usually slower
Neuromodulation acts via second messenger system whereas neurotransmission acts via ligand gated ion channels
NANC
Non-adrenergic and non cholinergic transmitters
Two types:
Ganglionic transmission:serotonin, GABA and dopamine
Post ganglionic terminal:Nitric oxide
Presynaptic modulation
Usually inhibitory
Co transmitters can affect transmitter release
post nerve terminal tissue
Activation of post nerve terminal tisssue cause biological response
Homotropic auto inhibition
Pre synaptic auto receptor activation causes inhibition of neurotransmitter release in cholinergic and adrenergic
hetrotropic presynaptic inhibition
Noradrenaline inhibits Ach in nerve terminals
rELEASE neurotransmitter x can act on another nerve terminal which can inhibit neurotransmitter Y and works in the opposite direction
Serotonin
Inhibits noradrenaline release and causes vasodilation and excitatory effect on eccentric neurones
Post synaptic medators
Mediators modify excitability
Mediator Y can also cause an individual effect by itself
But when and X and y act together they cause a strong effect
X and Y act on different tissues
NPY
NPY enhances the function of noradrenaline by increasing calcium
Co transmission of ATP and noradrenaline
Neuroadranaline and ATP are co stored in the vesicle at a ratio of 4:1
NA can also act on presynaptic a2 adrenoreceptor so GI coupled receptor can inhibit adynlayse cyclase inhibiting cAMP reducing calcium channel function reducing calcium
ATP
Stored in synaptic vesicle at terminals
Allows for fast transmission in autonomic ganglia
Co transmitter with noradrenaline causes contraction in bladder
Nitric oxide
Nitric oxide is synthesised from L-argine which is an amino acid
cGMP increases the vasodilation in the lungs
Sildenafil increases NO by inhibiting breakdown of cGMP(Localised effect)
Can reduce blood pressure which can cardiovascular reflex response to reduce vascocontrisction
