Autonomic Pharmacology Flashcards
What does the somatic afferent include?
Nerves supplying skin, joints, muscle
What does the somatic efferent include?
Neurons leaving spinal cord and enervating muscle (voluntary contraction)
What nervous system are the myenteric plexus and submucosal plexus part of?
ENS
What is a ganglion?
a collection of nerve cell bodies that lie outside of the CNS
Which system, parasympathetic or sympathetic uses ACh neurotransmitter for the preganglionic neurone and noradrenaline in the postganglionic neurone?
Sympathetic
In which are the axons shorter, pre or post ganglionic neurones?
Pre ganglionic neurones
What neurotransmitter does the parasympathetic system use for both preganglionic and postganglionic neurones?
ACh
State the 5 steps of neurochemical transmission.
-Uptake of transmitting precursor
-Synthesis of transmitter
-Storage of transmitter
-Depolarization by Action Potential
-Calcium ion influx through voltage activated calcium ion channels
-Calcium induced release of transmitter (exocytosis)
-Receptor activation
-Enzyme-mediated inactivation
OR
-Reuptake of transmitter
In sympathetic division of ANS, what does ACh open in the postganglion neurone and what does this cause?
Ligand-gated ion channels, causing depolarization and generation of action potentials
What does noradenaline activate in the sympathetic division?
G-protein coupled adrenoceptors
What does ACh activate in the parasympathetic division?
G-protein coupled muscarinic acetylcholine receptors
Where is muscarine found?
poisonous mushrooms
How many glycoprotein subunits do ligand-gated ion channels contain and what do these form?
5, and central ion conducting channel (each spans the cell membrane)
What do ligand-gated channels allow?
rapid changes in permeability of membrane to certain ions, alters membrane potential
How many binding sites are there normally for ACh receptors?
2
When the transmitter binds to the binding site on to the ion channel, does a conformational change occur immediately?
No, short delay
How many glyoprotein subunits are in an ACh receptor?
5
What are the steps of cholinergic transmission?
- Uptake of choline via transporter
- Synthesis of ACh via CAT
- Storage of ACh via transporter
- Depolarization by action potential
- Ca2+ influx
- Calcium ion induced release of ACh (exocytosis)
- Activation of ACh receptor subtypes (M1-M3)
- Degradation of ACh to choline and acetate by AChE, terminating transmission
- Reuptake and reuse of choline
What opens when 2 ACh molecules bind to receptor?
Sodium channel, creating graded depolarisation that can vary in amplitude
What is the name given to this graded depolarisation?
EPSP
What happens if depolarisation reaches threshold?
voltage-gated sodium ion channels open and nerve transmission occurs
Which is the only drug that affects cholinergic transmission at ganglia with any clinical significance?
Nicotine
What does nicotine mimic the effect of?
ACh
What does hexamethonium do and how?
Selectively blocks ganglionic transmission by open channel block (a form of non-competitive antagonism)
What are the most popular type of receptor in the body involved in chemical transmission?
G-protein coupled receptors
Which of these are G-proteins involved in: Rods and cones of retinas to allow sight; transduction of odors from curry to electrical signals
Both!
Are the receptor, G-protein and effector separate or combined proteins?
Separate
Is signalling via G-proteins fast or slow in comparison to transmitter-gated ion channels?
Slow
What type of membrane protein is the receptor?
Integral
What type of membrane protein is the G-protein?
Peripheral
What does the receptor protein consist of?
Single polypeptide with extracellular NH2 and intracellular COOH termini
How many transmembrane spans does the receptor contain and what are they joined by?
7, 3 extracellular and 3 intracellular connecting loops
What is it that allows the receptor to interact with the G-protein?
large intracellular loop and COOH tail
G-proteins consist of how many polypeptide subunits?
3
Which of the G-protein’s subunits can disassociate from the other two?
alpha
Where is the guanine nucleotide binding site in the G-protein and what can it hold?
alpha subunit, GTP or GDP
When G-proteins couple with receptors to cause a conformational change, the affinity of the binding site for what is reduced and what occurs?
GDP, so this dissociates from and GTP binds to the alpha subunit
What does the G-protein lose its affinity for after GTP binding?
Beta-gamma subunit, so alpha protein dissociates
What does the alpha subunit combine with to turn on or off action?
effector
What acts as an enzyme and what does it hydrolyse in G-protein function to turn off the signal?
the alpha subunit, hydrolyses GTP to GDP and Pi, to turn off signal
What are muscarinic receptors examples of?
G-protein coupled receptors
How many clinically important muscarinic receptors are there?
3 (M1,2,3)
Which receptors cause acid secretion in the stomach?
M1
Which receptors are present on the SAN?
M2
What do presynaptic autoreceptors mediate?
Inhibition of transmitter release (negative feedback)
If NA or ACh are released, what happens to amounts of Ca coming in?
Limited, decreased release of NA and ACh (negative feedback)
What does cocaine structurally resemble?
Noradrenaline
What transporter is noradrenaline recognised by?
U1
What do both amphetamine and cocaine cause?
vasoconstriction (alpha 1 stimulation) and cardiac arrythmias (B1 stimulation)
What does amphetamine structurally resemble?
Noradrenaline
What does Amphetamine inhibit?
MAO enzyme
What does amphetamine cause increased stimulation of?
Adrenoceptor
What does prazosin block?
alpha 1 (selective, competitive antagonist)
What is prazosin used for?
Anti-hypertensive agent. Vasodilates.
What does atenolol block?
B1
What is atenolol used for?
anti-anginal, anti-hypertensive
What does salbutomol do?
Selective agonist of B2. Used as bronchodilator in asthma
What is atropine used for?
To reverse bradycardia following MI and in anticholinesterase poisoning
What does atropine block?
Competitive antagonist of muscarinic ACh receptors (M1, M2 and M3 with equal affinity)