The sympathetic nervous system Flashcards
What is the structure of Acetylcholine, label the charges if there are any present?
What are the substrates of Acetylcholine?
The substrates are Choline and AcetylCoA
How is choline taken up into the nerve terminal?
By a choline transporter in the membrane, this is the rate limiting step for synthesis
What is the reaction for the production of Acetylcholine?
Whats the by product?
What enzyme is used?
AcetylCoA + Choline –> Acetylcholine + CoA
Enzyme: Choline Acetyltransferase (CAT)
How is Ach taken up in vesicles?
Are these pre or post synaptic vesicles?
What can this process be blocked by?
ACh is taken up into presynaptic Vesicles by an active transport process. This can be blocked by Vesamicol
What is ACh released in response to?
ACh is released in response to calcium entry into the presynaptic terminal
How is ACh inactivated?
What are the stages to this process?
- Following release into the synaptic cleft, ACh is available to active receptors
- The synaptic cleft is also rich in the enzyme Acetylcholinesterase which breaks ACh down into choline and acetic acid
- choline is taken back up into the nerve terminal by the choline transporter. this is blocked by Hemicholinium
What 3 compounds did dale use to characterise cholinergic transmission?
- Muscarine
- Nicotine
- Atropine
” two distinct types of action can be detected- a ‘muscarine’ action, paralysed by atropine, and a ‘nicotine’ action, paralysed by excess of nicotine”
What did Dale’s experiment show using ACh?
- It produces 2 different effects on blood pressure
- Why does the same compound triggers two dose-dependent opposite responses?
- Shows muscarinic and nicotinic receptors
Draw the parasympathetic organ synapse
Draw the structure of Muscarine
WIth muscarinic transmission, what is the main agonist?
Muscarine
Table showing how different drugs effect different chemicals actions
Tell me the effects that the agonists have on the below organ system when they bind to muscarinic receptors?
- Cardiovascular system
- Gastrointestinal actions
- Exocrine gland secretion
- Cardiovascular decreases HR, CO and vasodilation
- Gastrointestinal actions increased activity (GIT smooth muscle contracts and increased peristaltic activity)
- Exocrine gland secretion increased sweating, lacrimation and salivation (contracts bladder and bronchial smooth muscles; sweating, lacrimation, salivation, bronchial secretion)
Why does a decrease in HR and CO result in a sharp fall in BP?
mAChR result in release of NO which causes vasodilation
What is the treatment of acute angle-closure Glaucoma?
- parasympathetic innervation of constrictor pupillae
- parasympathetic innervation of ciliary muscles: use of pilocarpine in glaucoma to relieve pressure
- contracts ciliary muscle in the eye- this can help relieve increased intraocular pressure in glaucoma (commonest cause of blindness). (pilocarpine can be used)
What are the main muscarinic receptor subtypes and what type of receptors are they?
M1: Neural
M2: Cardiac
M3: Glandular
They are all G protein coupled receptors (GPCRs)
Tell me the following about the M1 receptor…
- Main location
- Cellular action
- Function
Tell me the following about M2 receptors…
Main location
Cellular action
Function
Tell me the following about M3 receptors
Main location
Cellular action
Function
What muscarinic receptors are stimulatory and which are inhibitory?
Stimulatory: M1, M3, M5
Inhibitory: M2 and M4
Muscarinic
Name the muscarinic receptor antagonists?
Atropine
Pirenzepine
What are the effects of muscarinic antagonists?
- inhibition of secretions
- effect on heart rate
- effects on the eye
- effects on the gut
- effects on other smooth muscle
- effects on the CNS
- CLINICAL USES
What are the receptors for ACh in the sympathetic and parasympathetic nervous system?
Muscarinic is the receptor in the parasympathetic nervous system
Nicotinic is the receptor in the sympathetic nervous system
What enzyme is used to break down the neurotransmitter ACh?
Acetylcholinesterase
Draw and explain nicotinic transmission at autonimic ganglia
What type of channels are nicotinic receptors and what are they permeable to?
All nicotinic receptors are ligand-gated ion channels are are permeable to cations
Whats different with the nicotinic receptors compared to those from the muscle?
The isoform at the ganglia is different from the muscle
When ACh binds to the nicotinic receptor, what movement of ions occurs?
Na+ are imported and K+ exported
Tell me the structure of the ligand-gated ion channels
- 5 subunits
- 2x alpha, 1x beta, 1x delta and 1x gamma
- alpha subunits contain the binding sites for ACh
- When Ach binds to binding sites in alpha subunits, the ion channel opens, and changes permeability and drives change In current in post synaptic axon
What are the types of nicotinic receptors and where are they found?
- N2 is also called NN as it is based at neurons
- N1 is also called NM as it is found at neuromuscular junctions
Name some nicotinic receptor agonists
- Acetylcholine
- Nicotine
- Dimethylphenylpiperazimium (DMPP)
Identify the structures of each of these nicotinic receptor agonists
What are the effects of nicotine and DMPP ?
Nicotine: stimulation of autonomic ganglia
EMPP: stimulation of autonomic ganglia. DMPP is a non-natural drug used to agonise nicotinic receptors
Name a nicotinic ganglionic recetor antagonist
What compound blocks ganglionic nicotinic receptors
Hexamethonium
What is the cat nictitating membrane?
A third eyelid (the sideways eyelid). Cats have 2 sets of eyelids, the ones that go up and down and always a sideways eyelid. This protects from night vision and to keep the eye moist all the time to help with night hunting and general eye function
What does this experiment tell you about the action of hexamethonium?
- Took a cat, study both left and right eye at the same time
- Look at one eye for stimulation of preganglionic site e.g. left eye
- Postganglionic neuron Is removed for superior cervical ganglion in the other eye e.g. right eye
- Dots indicate electrical stimulation
- Top shows recording of blood pressure so can study the physiological consequences
- Stimulate pre and post ganglionic sites and get contraction of nictitating membrane and drop in BP
- Apply nicotine instead, sees drop in preganglionic neuron, but still contraction
- Post doesn’t have ganglion has been removed so no contraction seen there
- Apply adrenaline, directly stimulating membrane. Therefore, doesn’t matter if preparation is intact (with ganglion) or not as still causes a contraction
- Apply C6, antagonist of nicotinic receptor, try to repeat stimulation with nicotine after. Not seeing same stimulation as before. No longer see any response at pre- therefore indicating there’s something in ganglion that activated by nicotine that’s now blocked by C6. When apply with adrenaline still causes response so shows that C6 was a nicotinic receptor antagonist
Whats are the pharmacological actions of hexamethonium?
- Blocks the nicotinic receptor- no agonist action
- Reduces blood pressure (beneficial for hypertension)
- Dry mouth
- reduced gastric acid secretion
- Constipation
- Urinary retention
- Blurred vision
- Postural Hypotension
- Sexual dysfunction
Whats series of compounds does Hexamethonium belong to?
How are they named?
Belongs to a series of compounds known as polymethylene bismethonium
They’re names depending on the number of carbons in their chain
What experiment did Paton and Zaimis do with polymethonium?
- Paton and Zaimis compared the effect of polybismethonium compounds at autonomic ganglia and neuromuscular junction
- Balance of affinity and potency for good pharmacological agents
