Cholinergic Transmission Flashcards
What are the different types of cholinergic receptors? Where are they located? What are the other types of receptors?
somatic nervous system
- releases acteylcholine which binds to the nicotinic receptors
- skeletal muscle
parasympathetic nervous system
- pre and post synaptic release acetylcholine which binds to muscarinic receptors
sympathetic nervous system
- pre ganglion releases acetylcholine which binds to nicotinic receptors
- post ganglion can release acetyl choline which binds to muscarinic receptors or noradrenaline (sweat gland) which binds to alpha/beta adrenergic receptors
sympathetic nervous system = adrenal medulla
- pre ganglion releases acetylcholine which binds to nicotinic
- no post ganglionic. adrenal medulla releases noradrenaline
Where are the nicotinic and muscarinic receptors found?
nicotinic receptor
- in the neuromuscular junction of skeletal muscles
- in adrenal medulla
- on all post ganglionic nerve cell bodies of ANS before it goes to the muscarinic in the target organ
- are coupled with ion channels
muscarinic receptor
- on the target organs of the body receiving acetylcholine from the parasympathetic system
= cardiac, smooth, glands
- are G protein coupled
What are the agonist for the nicotinic and muscarinic receptors?
acetylcholine and related choline esters are agonist at both the muscarinic and nicotinic receptors
more potent at the muscarinic receptors
What are examples of agonists acting at muscarinic receptors? What is their effect?
cardiovascular (M2)
- cardiac slowing = decrease in cardiac output
- generalised vasodilatation
smooth Muscle
- smooth muscle other than vascular smooth muscle (controls BP), contracts
= GI tract, bladder and bronchial smooth muscle
sweating, lacrimation, bronchial secretion
- stimulation of exocrine glands
What is glaucoma? How are agonist of muscarinic receptors used to treat glaucoma?
glaucoma
- pressure in the eye is high due to build up of fluid
affects the ciliary muscle and the constrictor pupillae
- ciliary muscle contraction causes reduction in tension of suspensory ligaments of lens, causing lens to bulge, reducing its focal length
binds to muscarinic receptors and stimulates Ach effect
What is an examples of an antagonist of the muscarinic receptor? What are the side effects?
atropine
atropine poisoning
Mad as a hatter
- excitatory effect
- low doses = mild restlessness, high doses = agitation and disorientation
Blind as a bat
- pupils are dilated and unresponsive to light
Dry as a bone
- affects salivary glands and skin = decreased salivation, dry mouth
Red as a beet
- marked flush (redness)
Hot as a pistol
- elevated body temperature
What type of stimulate occurs if muscarinic receptors are blocked by atropine?
effects are similar to nicotine
- due to stimulation of the autonomic ganglia of the sympathetic system
How is acetylcholine synthesised, stored, released and degraded?
choline combines with acetyl to form acetylcholine
- catalysed by choline acetyl transferase
acetylcholine is stored in vesicles
action potential/electrical impulse causes release of acetylcholine into the synaptic cleft
acetylcholine binds to the receptor on the post synaptic membrane
binding causes the opening of the ligand gated receptor (fast opening)
- nicotinic receptor is directly coupled with the cation channel
Na-K+ go down the concentration gradient. electrical impulse resumes and continues across the new neurone
- sodium moves out
- potassium moves in
- depolarisation occurs
acetylcholinesterase hydrolyses acetylcholine into acetate and choline
choline is taken back into the pre synaptic membrane by a choline transporter
What is the structure of nicotinic receptors?
have 2 binding sites for acetylcholine
all cholinergic receptors are pentamers
- have alpha, beta, gamma, delta and alpha subunits
can exists in more than one form
are ligand gated channels
- are directly coupled with ion channels
Where can nicotinic receptors be found? What is the difference between nicotinic receptors at neuromuscular junction and the autonomic ganglion?
location?
agonist?
antagonist?
nicotinic receptors are at the neuromuscular junction, autonomic ganglion and various sites in the CNS
neuromuscular junction
- skeletal neuromuscular junction = mainly post synaptic
- excitatory response, increases cation channels permeability
- agonist = acetylcholine
- antagonist = atracurium
autonomic ganglion
- autonomic ganglia = mainly post synaptic
- excitatory response, increases cation channels permeability
- agonist = acetylcholine
- antagonist = hexamethonium
What are the physiological effects of nicotine binding to the cholinergic receptors?
stimulates both the sympathetic and parasympathetic nervous system
symptoms
- tachycardia = increases heart rate
- GI motility and secretions
- increased bronchial, salivary and sweat secretions
Which antagonist affect acetylcholine? How can antagonist act to block acetylcholine? What is the effect? synthesis storage release degradation
block acetylcholine release from vesicles
- muscle paralysis
block choline re-uptake into the pre synaptic membrane
- interferes with synthesis
- high levels of choline stimulate the acetylcholine receptor to stay open
= paralysis of nerve impulse, no rush of cations in the channel
cholinesterase inhibition
- hydrolyses acetylcholine = terminates action
- acetylcholine builds up, receptor stays open
= causes equilibrium of Na-K+ therefore induces depolarising block
= leads to bradycardia (slow HR), hypotension)
What is myasthenia gravis?
muscle weakness and increased fatiguability due to failure of neuromuscular transmission
- loss of nicotinic acetylcholine receptors due to auto antibodies binding with acetylcholine receptors = stops acetylcholine binding
How can myasthenia gravis be treated?
can be treated by anti-cholinesterase or tubocurane
tubocurane
- restores transmission following reversible competitive antagonism of the receptor
anti-cholinesterase
- acetylcholine builds up as it is not hydrolysed/degraded
- high concentration of acetylcholine competes with/displaces auto antibodies
