MEMBRANES AND RECEPTORS MODULE

PRESENTATION ASSIGNMENTS

AIMS
The presentation assignments are designed to cover important material in this course, much of which will
complement work in other sessions, particularly those centred on the Autonomic Nervous System later in
the module. The format of the assignments will develop your skills in researching and distilling new
information and give you valuable experience in preparing and delivering specific scientific information at
an appropriate level through oral presentation.

ORGANIZATION
(1) Students will work in their normal study groups.
(2) Each study group will be given one topics to research, see tables attached
(3) Groups will decide who will be responsible for delivering each of the assignment presentations in the
form of a 10 min talk. Different students should make the presentations in Session 6 and Session 7.
(4) Each talk will be given to groups of approximately 40 students and a tutor. Presenters should note that
their presentations are a learning opportunity for their peers and, hence, that it is important to
emphasise the core concepts in the subject material, rather than to go into too much detail to
„impress‟ the tutor.

Teamwork: It is very important that study groups work together in researching and preparing the material
for each assignment presentation. In addition, it is important that each oral presentation is practised in
one or more “dummy-runs” within the group. This allows the presenter(s) to practise his/her
presentation, the group a chance to suggest improvements, and crucially, to ensure that the length of the
presentation fits the 7-8 min time-slot allowed. Presentations will be stopped by the tutor if they overrun
their allotted time. It should be noted that it is the responsibility of the whole group, not just the
presenter(s), to field questions about the presentation asked by either other students or the tutor.

The Assignments: To help you structure your presentation a work book is provided outlining issues which
should be addressed in each of the talks. This format should also help you to take relevant notes during the
presentations.

Visual Aids: Presentations will be scheduled in tutorial rooms equipped with a computer and data
projector to permit PowerPoint presentations to be made. You should aim to make your presentation with
a minimum number of slides. A good rule-of-thumb is 7 slides for a 10 minute presentation; therefore 5
slides should suffice.
Peer support for student learning:
Handouts: If students have wish to provide handout materials to facilitate note taking for their audience.
Please note that there are no Faculty funds allocated for this purpose, and so any costs incurred in this way
cannot be reimbursed.
WebBoard: Alternatively, some students have posted their notes or PowerPoint presentations on the
module WebBoard. This is encouraged. To assist those wishing to locate such materials within the
WebBoard, it would be helpful if all resources for the same presentation could be posted together
under the same topic, e.g. „Presentation ACh1‟, „Presentation ACh2‟, etc..

Assessment of assignment presentation content: New subject material is presented by your peers during
assignment sessions which illustrates core material and adds further detail. A commonly asked question is
„Will I need to know the subject material covered by the assignment sessions for the second SAQ
asessment in the module?‟ While it would be possible to achieve a satisfactory grade in the second
assessment by revising only the core material presented in the module, the assignment sessions are
designed to provide additional important details and integration within the module. Thus, good satisfactory
or excellent answers to an SAQ question may well1 include information from these sessions.
 SESSIONS 6 AND 7 – PRESENTATIONS
ACETYLCHOLINE

Acetylcholine is a very important neurotransmitter in both the central and peripheral nervous
systems. Elsewhere in this and other modules, you will consider the role of acetylcholine at the
neuromuscular junction - the neuroeffector junction of the somatic nervous system - in some detail.
Therefore, for the purposes of these assignments we will concentrate on acetylcholine as a
transmitter in the autonomic nervous system (ANS). Clearly much of what we learn with respect to
acetylcholine in the ANS is also applicable to this molecule acting as a transmitter in other systems.

PRESENTATION ACh1

Synthesis & Storage:

(1) Acetylcholine acts as the major neurotransmitter at four distinct general classes of synapse
in the autonomic nervous system. One such class of synapse is at the post-ganglionic fibre-
target tissue (neuroeffector) junction of the parasympathetic branch of the ANS; what are
the other three classes? Draw a simple diagram to illustrate where acetylcholine acts as the
major neurotransmitter in the ANS.

(2) Acetylcholine is synthesised from choline (an essential component obtained in the diet) and
what other metabolic intermediate? What is the enzyme involved and where does synthesis
occur?

(3) How is acetylcholine "packaged" for release?

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Regulation of Release:

(4) Parasympathetic discharge is primarily regulated by CNS initiation of the firing of pre-
ganglionic fibres which form synapses with the post-ganglionic neurones. Use the outline
given below to sketch the events which occur to cause release of acetylcholine by pre-
ganglionic cholinergic fibres synapses.

(5) Give an example of an agent which interferes with the release of acetylcholine.

How is Neurotransmitter Action Terminated?

(6) For a neurotransmitter such as acetylcholine to act efficiently (i.e. for post-synaptic effects to
be exerted on a sub-second time-scale), the parasympathetic synapse must possess
mechanisms to rapidly terminate the action of acetylcholine. How is this achieved?

(7) What happens to free choline and acetate present in synapses?

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PRESENTATION ACh2

Cellular Targets:

(1) Briefly list some of the important sites (i.e. organs/tissues) of parasympathetic innervation.

(2) What is the effect of increased parasympathetic discharge in the heart?

(3) Acetylcholine is employed as the neurotransmitter at all parasympathetic nerve synapses.

Are there any other synapses in the autonomic nervous system that use acetylcholine as
neurotransmitter?

Cholinoceptors:

(4) Multiple forms of receptors for acetylcholine, termed "cholinoceptors", occur. What
naturally-occurring substances, which each either mimic or prevent some of the actions of
acetylcholine, were first used to show that two distinct classes of acetylcholine receptor
exist?

(5) Briefly, explain how the receptor subtype found at the ganglionic junction causes a post-
ganglionic response when activated by acetylcholine.

(6) What is the class of acetylcholine receptor found at the parasympathetic neuroeffector
junction?

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(7) This class of acetylcholine receptor be further divided into at least three subtypes Each
mediates its cellular action by changing the activity of enzymes which synthesise second
messengers, and/or by changing the opening of particular ion channels in the plasma
membrane. Indicate in the table below the predominant G-protein and effectors that are
involved in transducing the signal from different receptor subtypes List these acetylcholine
receptor subtypes and which enzymes/ion channels each sub-type preferentially links to:

Subtype G Protein? Effector? Activation or Inhibition?

M1

M2

M3

(8) Briefly describe the series of events that couple activation of M2 muscarinic receptors to the
activation of the effector(s).

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PRESENTATION ACh3

Physiologically important actions of acetylcholine:

(1) Release of acetylcholine by parasympathetic post-ganglionic fibres plays an important role in

the regulation of a number of tissues. For the tissues given below list the major physiological
actions of acetylcholine.

Tissue Predominant Major physiological action?

receptor
subtype?
Sinoatrial node

Bronchi

Bladder

Glands

Parasympathetic nerve
terminals at neuroeffector
junctions, i.e. „presynaptic
receptors‟

Cholinoceptor Pharmacology:

(2) Agents which mimic some or all of the actions (i.e. cause the same cellular responses) of
acetylcholine are termed cholinoceptor agonists. What might be the advantage of
synthesising cholinoceptor agonists which only interact with a particular receptor subtype?

(3) Are such agents available?

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(4) If so, are they used clinically

Agents which can prevent the actions of acetylcholine are termed cholinoceptor antagonists. If the
action of such agents is competitive, then the antagonist interacts with the cholinoceptor, occupying
or blocking the agonist binding site, but having no stimulatory effect on cholinoceptor activity per se.

(5) Muscarinic cholinoceptor antagonists are used therapeutically in a number of clinical

conditions.One clinical use of muscarinic cholinoceptor antagonists is to treat
gastrointestinal disorders. Also, these agents are frequently given as a premedication for
general anaesthesia. Why are muscarinic cholinoceptor antagonists used under these
circumstances?

Therapeutic use Reason for use

Gastrointestinal disorders

Premedication

(6) What unwanted side effects limit the usefulness of these agents?

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PRESENATION ACh4

How does understanding the autonomic innervation of the eye help to explain the strategies used to
treat glaucoma?

(1) Draw a simple diagram to illustrate the anatomy of the human eye relevant to sites of
sympathetic and parasympathetic innervation.

(2) An abnormally raised intraocular pressure is termed glaucoma. Untreated this can lead to
irreversible damage of the eye and blindness. What are the most likely causes of this
condition?

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(3) What are the consequences of increasing parasympathetic tone in the eye? Might this be
beneficial in decreasing intraocular pressure?

(4) Which receptor ligands are used clinically to treat glaucoma?

(5) If the desired effect is to increase the stimulation of muscarinic receptors, what alternative
non-receptor strategy can be adopted. Which agents are used clinically?

(6) What are the effects of increasing sympathetic tone in the eye? Is this most likely to lead to
an increased or decreased intraocular pressure?

(7) What agents, active at adrenoceptors, are used clinically in the treatment of glaucoma?

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 SESSIONS 6 AND 7 – PRESENTATIONS

NORADRENALINE

Noradrenaline is an important neurotransmitter in the central and peripheral nervous systems. For
the purposes of these assignments we will concentrate on noradrenaline as a transmitter in the
autonomic nervous system (ANS). Clearly, much of what we learn with respect to noradrenaline in
the ANS is also applicable to noradrenaline acting as a central transmitter.

PRESENTATION NA1

Synthesis & Storage:

(1) Consider the following: "Noradrenaline is the major neurotransmitter at the neuroeffector
junction of sympathetic post-ganglionic fibres" - Using a simple schematic diagram of the
autonomic nervous system, explain this statement.

(2) Are there any post-ganglionic synapses in the sympathetic nervous system at which
noradrenaline is not the transmitter?

(3) The "biogenic amines" (dopamine, noradrenaline and adrenaline) are all synthesised from
the amino acid tyrosine: outline the synthetic pathway. What are the enzymes involved?
Where does this pathway occur?

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(4) What determines whether a nerve terminal is "dopaminergic" (releases dopamine) or
"(nor)adrenergic" (releases noradrenaline)?

(5) How is noradrenaline “packaged” for release?

Regulation of Release:

(6) Sympathetic discharge is primarily regulated by central nervous system (CNS) initiation of
the firing of pre-ganglionic fibres which form synapses with the noradrenergic post-
ganglionic neurones. Briefly outline the sequence of events which occur following release of
acetylcholine by the pre-ganglionic fibre which lead to noradrenaline release. Use the
sketch of a noradrenergic synaptic varicosity below to briefly outline the key features of
post-ganglionic sympathetic innervation of target issues.

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PRESENTATION NA2

Cellular Targets:

(1) Briefly list some of the important sites (i.e. organs/tissues) of sympathetic innervation.

(2) In the heart, increased noradrenaline release causes both an increase in heart-rate (positive
chronotropy) and an increase in the force of each contraction (positive inotropy). Explain
the anatomical basis for these two distinct responses to sympathetic innervation.

Adrenoceptors:

(3) Multiple forms of receptors for noradrenaline (and adrenaline), termed "adrenoceptors",
occur. All adrenoceptors belong to the family of receptor proteins whose primary amino
acid sequence crosses the plasmalemma seven times and which exert their cellular effects
by activation of sub-populations of G proteins (guanine nucleotide binding proteins) within
the cell. Complete the Table overleaf to show which effector molecules (e.g. adenylyl
cyclase, phospholipase C, etc.) are regulated by the different subtypes (i.e. 1-, 2-, 1- and
2) of adrenoceptor. Are distinct types of G protein involved in linking different receptor
subtypes to each effector?

Receptor subtype G protein? Effector? Activation or inhibition?

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How is Neurotransmitter Action Terminated?

(4) For a neurotransmitter such as noradrenaline to act efficiently (i.e. for post-synaptic effects
to be exerted on a sub-second time-scale), the sympathetic synapse must possess
mechanisms to rapidly "clear" noradenaline from the synaptic cleft. How is noradrenaline
removed from the synaptic cleft? Outline some of the properties of the mechanism which
allows it to rapidly decrease extracellular noradrenaline levels.

(5) What is the fate of noradrenaline removed from the synaptic cleft? Can noradrenaline be
re-packaged for re-use?

(6) Name the TWO major enzymes responsible for inactivation of noradrenaline?

(7) Which products of metabolism can be measured in the blood or urine as an indirect index
of sympathetic activity?

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PRESENTATION NA3

Physiologically important actions of noradrenaline:

(1) Complete the following Table illustrating the major physiological effects of adrenoceptor
activiation. The predominant actions of adrenoceptor stimulation in liver and fat are given
as examples.

Tissue Adrenoceptor Physiological response

subtype
involved

Liver 1 glycogenolysis
2 glycogenolysis

Smooth muscle: Vascular

Airways

GI-tract

Bladder

Heart: SA-node

Ventricle

Adipose tissue 1/β3 lipolysis

Skeletal muscle

Iris

(2) Does the hormone adrenaline contribute to, or exert the predominant effect for, any of the
effects you have listed above?

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Adrenoceptor Pharmacology

(3) Agents which mimic some or all of the actions (i.e. cause the same cellular responses) of
noradrenaline/adrenaline are termed adrenoceptor agonists. What might be the
advantage of synthesising an adrenoceptor agonist which only interacts with a particular
receptor subtype?

(4) Outline the type of adrenoceptor agonist used to:

Therapeutic intervention Type of adrenoceptor Drug of choice

agonist
Reverse bronchoconstriction in asthmatics

Aid decongestion of the nasal passages

Prolong the action of a local anaesthetic

(5) Why are different agents required for these different therapeutic interventions?

(6) Agents which can prevent the actions of catecholamines - adrenoceptor antagonists - do so
by interacting with adrenoceptors, blocking agonist binding, but having no stimulatory
effect on adrenoceptor activity per se. Adrenoceptor antagonists are widely used
therapeutically in a number of clinical conditions (and will be covered in other parts of the
Module). Give an example of the clinical use of an - and -adrenoceptor antagonist.

Receptor Antagonist Clinical use

subtype
α

(7) what unwanted side-effects are important in limiting the usefulness of these agents?

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PRESENTATION NA4

α-Methyltyrosine, α-methyl DOPA and guanethidine have been used clinically to inhibit
sympathetic neurotransmission. Explain the mechanism by which each of these agents affects
noradrenaline release, and why their clinical usage has declined.

(1) Which enzyme is specifically inhibited by α-methyltyrosine? Why is this important with
respect to noradrenaline synthesis?

(2) What particular type of cancer is treated by administration of α-methyl tyrosine?

(3) Instead of acting as an inhibitor, -methyl DOPA acts as a “false substrate” for which
biosynthetic enzyme? What product of -methyl DOPA metabolism accumulates in
noradrenergic terminals? If released what is the major action of this “false transmitter”?

(4) α-methyl DOPA has been adopted as one clinical strategy for the treatment of hypertension;
explain the theory behind this therapeutic approach.

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(5) Guanethidine is a noradrenergic neurone blocking drug – what does this mean? Briefly
outline the hypotheses put forward to explain how guanethidine inhibits noradrenaline
release.

(6) Guanethidine is no longer used clinically – what unwanted side effects caused withdrawal
of
this agent?

(7) Generally, the preferred tools for inhibiting noradrenergic transmission act at
adrenoceptors – why do you think adrenoceptor agonists and antagonists have become the
drugs of choice?

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