Fall 10 - ANS Flashcards
(73 cards)
Why does the autonomic innervation of the sweatglands present an interesting case for pharmacology of the ANS?
Since the sweatglands’ sympathetic fiber uses ACh as its transmittor substance they are pharmacologically affected in the same way as para-sympathetically innervated organs.
List the different receptor subcategories of the para-sympathetic and sympathetic part of the ANS.
Para-sympathetic:
- nicotinergic (ionotropic)
- muscarinic (metabotropic, M1/M2)
Sympathetic:
- adrenergic (GPCR)
- α1
- α2
- β1
- β2
- β3
Is the fast breakdown of ACh in the synaptic cleft essential for ANS?
No. However in the motoric end plate this feature is essential for allowing dynamic wilful use of skeletal muscles.
Compare the recycling of ACh with noradrenaline in the presynaptic membrane and synaptic cleft.
ACh: Exocytosis - (acetylcholinesterase) - acetate + choline - re-uptake of choline (high affinity re-uptake mechanism) - synthesis - storage - …
Noradrenaline: (tyrosine - aided diffusion - synthesis - )exocytosis - re-uptake - lysis/packaging - …
Compare the catalytic enzymes of ACh with those of noradrenaline.
ACh
- acetylcholine esterase: (postsynaptic)membrane bound, highly effective
Noradrenaline
- MAO (monoamine oxidase): relatively ineffective, resides in mitochondria of presynaptic neurone
- COMT (cathecole-O-methyltransferase): relatively ineffective, partially free in cytoplasm, partially membrane bound
What is the role of autoreceptors in the sympathetic and para-sympathetic nervous system?
Autoreceptors generally communicate negative feedback for synaptic transmission.
Sympathetic:
- α2-receptors are the main autoreceptor, inhibiting further NA release when bound to NA (mimic blockage of postsynaptic adrenergic receptors)
Para-sympathetic:
- muscarinic receptors (M2) act, similarly to α2-receptors in the sympathetic presynaptic membrane, on the presynaptic paradympathetic membrane
(contrarily, in skeletal muscles the autoreceptors of the motoric endplate synapses act to further induce release of ACh)
What are heteroreceptors?
Presynaptic membrane receptors that bind other transmittor substances than those emitted into the synapse, e.g.
- muscarinergic receptor on sympathetic presynaptic membrane allows para-sympathetic nerves to inhibit sympathetic ones
- vice versa, with α2-receptors found on presynaptic memebrane in para-sympathetic nerves
- both aforementioned require ongoing main transmittor substance-exocytosis in order to work
- PG (prostaglandine receptors) are found on sympathetic nerves’ presynaptic membrane
- adrenaline via the systemic circulation acts upon α2-receptors in both ANS subsystems
How is impulse frequency-based cotransmission energy saving? Give an example.
E.g. NPY co-release with NA is governed so that NA/NPY co-vesicles are released only when action potential frequency rises over a certain value, as opposed to only NA containing vesicles during lower frequency action potentials. As NPY synthesis is relatively more energy-expending (in the soma) than NA synthesis (in the presynaptic bulb), and NPY/NA are more effective than separate, it makes more sense to perform co-release only when a greater response is wished (greater frequency of action potentials).
What is the basis for the difference in amine (ACh) and peptide transmittor substance (LHRH) elimination from the synaptic cleft in para-sympathetic synapses?
The difference lies in elimination routes:
- ACh is eliminated effectively by acetylcholinesterase
- LHRH does not have an equally effective elimination route
Give an example of a cotransmission target organ resulting in distinctly different effects in the target tissue.
Parasympathetic fibers of the salivary glands increase salivation through action of ACh, but simultaneously cause vasodilation with the release of VIP (vasoactive intestinal polypeptide).
Why is atropine not able to block the effects of nicotine on nicotinergic ACh-receptors?
The receptor has a higher affinity for nicotine than for atropine (?).
What results from administering a high dose of ACh to a patient which has previously received atropine?
Activation of ANS ganglia and sympathetic NS (high bp, low heart rate, watery salivation, glandula suprarenalis adrenaline release etc.)
Through which mechanism does ACh lower blood pressure when administered iv?
Smooth muscle cells of the endothelium exhibits ACh-receptors which when activated stimulate NO production which seizes contraction of the smooth muscle cells.
Why does iv ACh induce sweating?
The postsynaptic parasympathetic fiber that innervated the sweatglands function exceptionally via muscarinic ACh-receptors.
Explain the following terminology as pertaining to heart function:
- chronotropic
- dromotropic
- ionotropic
chronotropic: pulse
dromotropic: atrioventricular conduction
ionotropic: contraction force
What are the different muscarinic ACh-receptor subcategories and in what tissues are they found?
M1: encephalic tissue, possible target for Alzheimer medication
M2: cardiac, mediate vagal stimuli
M3: glandular tissue, also mediates ACh effect on endothelium
(M4: basal ganglia)
(M5: substantia nigra)
Why do neuronal and skeletal muscle nicotinergic ACh-receptors differ in their function, and how?
Neuronal nicotinergic ACh-receptors allow a greater passage of Ca-ions than skeletal muscle receptors. The difference is a result of the difference in the 5-part protein configuration that makes up the receptors ion channel (α+β subunits in the neuronal channel, α+β/γ/δ etc. in skeletal muscle channel).
What part of the nicotinergic ACh-receptor binds ACh?
Only the α-subunits bind ACh.
What is the difference in the mechanism of action of competitive inhibition (e.g. tubokurariini) and non-competitive inhibition (e.g. heksametoni) for the nicotinergic ACh-receptor?
Whilst tubokurariini binds to an α-subunit on the surface of the receptor, the non-competitive inhibition by heksametoni is mediate by binding inside the ion channel. The latter thus cannot be displaced by an excess amount of ACh.
Explain depolarising blockage using succinyl choline (suksametoni, diatsetyylikoliini) as an example.
Succinyl choline binds to the motorneurone/muscle plate synapse, activating nicotinergic ACh-receptors. Succinyl choline however doesn’t release from the receptor, causing prolonged depolarisation of the postsynaptic membrane. This causes voltage-gated Na-ion channels to inactivate and remain so, inhibiting further action potential transduction.
How is depolarizing blockage attained with ACh?
Depolarizing blockage can also be reached with ACh if ACh breakdown is inhibited, by for example an anticholinesterase.
Explain desensitization for nicotinergic ACh-receptors.
Desensitization, or phase II blockage, occurs following prolonged exposure of receptors to the agonist. When desensitized, the postsynaptic membrane is not able to respond to agonist stimuli even after the membrane potential has returned to normal.
What is the rate determining step of the choline recycling in the synapse?
The availability of choline, i.e. the speed of the re-uptake of it from the synaptic cleft. (N.B. not the speed of cholineacetyltransferase, plasma availability usually 10 μmol/l).
What might be a function of the release of ACh-quantas and MEPPs (miniature end plate potentials)?
The function might be that of a receptor-gathering signal, retaining receptor density at the motoric end plate.
