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ESA2 Callum's Cards - Complete > M&R S6 - Receptors and Membrane Turnover + Presentation Content (S7 included) > Flashcards

M&R S6 - Receptors and Membrane Turnover + Presentation Content (S7 included) Flashcards

1
Q

How are chemical signals classified?

A

By their function

Hormones:
Signalling between cells via the circulatory system

Neurotransmitters:
Signalling at synapses

Local chemical mediators:
Signalling between adjacent cells in the same tissue

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2
Q

What is a ligand?

A

Any small molecule that binds specifically to a receptor site

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3
Q

What are the two major types of ligand and what are their functions? (broadest terms)

A

Agonists:
Activates receptors

Antagonist:
Binds without causing activation of receptor

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4
Q

What is a receptor?

A

A molecule that recognises specifically a second molecule (ligand) or group of molecules and in response to binding brings about the regulation of a cellular process

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5
Q

How are receptors classified?

A

According to the agonist that they recognise

Sub classification can be made on the basis of their affinity to a series of antagonists

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6
Q

What is the difference between a receptor and an acceptor?

A

An receptor is always functionally silent when unbound

A ‘receptor’ that operates in the absence of its ligand is an acceptor

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7
Q

What is meant by ‘signal transduction’?

A

When a ligand binds to a receptor (the signal) a physiological response is generated

(signal results in action - transduction)

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8
Q

How is signal transduction performed with hydrophobic and hydrophillic molecules?

A

Hydrophobic:
Ligand diffuses through cell membrane and binds to a cytoplasmic or organellar receptor, eliciting a response

Hydrophilic:
Ligand cannot diffuse through the cell membrane and binds to a cell surface receptor, eliciting a response

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9
Q

What governs the responsiveness of a cell to a signalling molecule?

A

Presence of absence of a specific receptor

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10
Q

What similarities are there between enzymes and receptors?

A

Both have specific binding sites

Specificity governed by shape of binding cleft

Specificity of binding confers specificity of action

Binding often reversible in both

Ligand binding (receptor) and allosteric regulator binding (enzyme) both induce conformational change and change in activity

No chemical modification of ligand or allosteric regulators

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11
Q

What are the differences between receptors and enzymes?

A

Affinity:
- Affinity of ligand binding to receptors is typically higher. The concentration of ligand that fills half of available receptors (KD - Disassociation constant) is generally nanomolar to micromolar (10-9 to 10-6)

  • Affinity for substrate binding to enzymes is lower. The concentration of a substrate that fills half of all available active sites on enzymes (KM - Michaelis constant) is generally micromolar to millimolar (10-6 to 10-3)

Chemical modification:
- Enzymes catalyse chemical modification of the substrate when bound to an active site, Receptors do not chemically modify ligands

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12
Q

Give some examples of processes that receptors are involved in

A

Signalling by hormones and local mediators

Neurotransmission

Cellular delivery (Apoprotein E receptors and LDL)

Control of gene expression (thyroid hormone receptors)

Release of intracellular calcium stores (IP3-R)

Immune responses

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13
Q

What are some common mechanisms by which extracellular hydrophilic signals are transduced into a cellular event

A

Membrane bound receptors with integral ion channels

Membrane bound receptors with integral enzyme activity

Membrane bound receptors which couple to effectors via transducing proteins

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14
Q

Describe the general action of membrane bound receptors with integral ions channels

A

Agonist binds to the ligand gated ion channel

This results in a conformational change and the opening of the gated channel

The channel then permits flow of ions down the electrochemical gradient

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15
Q

What are the two types of membrane bound receptor with integral ion channels (ligand gated ions channels)?

A

Classical

Non-classical

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16
Q

Describe the structure of classical membrane bound receptors with integral ion channels (ligand gated ions channels)

Give an example of a receptor with this structure

A

Pentameric subunits
4 transmembrane domains

Nicitonic Ach receptors (nAchR)

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17
Q

Give an example of a non-classical membrane bound receptor with integral ion channel

A

Ryanodine receptors (Ca2+)

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18
Q

Describe the general action of membrane bound receptors with integral enzyme activity

Give some examples of such receptors

A

Agonist binds to the extracellular domain of these receptors

Causes a conformational change which activates intrinsic enzyme activity

This ‘enzyme’ is contained within the structure of the receptor

For example:
Platelet derived growth factor linked directly to tyrosine kinase
Insulin receptor

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19
Q

Describe how tyrosine kinase linked receptors initiate cellular response to the binding of a ligand

A

Tyrosine kinase linked receptors autophosphorylate upon ligand binding

Phosphorylated tyrosine residues are then recognised by:
- Transducing proteins
E.g. Insulin receptor substrate-1 (IRS-1)
- Enzymes
E.g. Src homology-2 (SH-2) domains

On association with receptor or transducing protein effector enzymes are activated by:

  • Tyrosine phosphorylation (in the case of direct association with the receptor)
  • Allosterically (when the transducing protein binds the the receptor)

This transduces the message into an intracellular chemical event

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20
Q

What is another name for membrane bound receptors with transducing proteins?

A

G-protein coupled receptors
OR
Seven transmembrane domain receptors

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21
Q

Describe the structure of a membrane bound receptor with transducing proteins (GPCR)

A

Contain 7 transmembrane domains, a ligand may bind here

The N terminal end is extracellular, a ligand may bind here

The C terminal end is cytoplasmic, this is the G-protein coupling domain

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22
Q

How do G-protein coupled receptors operate?

A

Ligand binds to a receptor on the extracellular N terminal region or between the transmembrane regions

The G-protein will then dissociate and signal an effector, this can be an ion channel or an enzyme

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23
Q

Give some examples of membrane bound receptors with transducing proteins

A

Muscarinic Ach receptors
Dopamine receptors
5-HT receptors
Light, smell and taste receptors

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24
Q

How does the action of G-proteins on an effector vary and what effect does this have?

A

Can be stimulatory or inhibitory

Can often have an effector that is stimulated and inhibited simultaneously by different G-proteins

This is ‘Integrated signalling’ where the two signals combine to produce a measured effect

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25
Q

Give some examples of hydrophobic ligands

A

Steroids (Cortisol, oestrogen, testosterone)

Thyroid hormones

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26
Q

How do intracellular receptors appear in their resting state?

A

Bound to heat shock or chaperone proteins

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27
Q

Describe what happens when an intracellular receptor is activated

A

Hydrophobic ligand binds

Activated receptor dissociates from the stabilising protein and translocates to the nucleus

This is where it binds to control regions of DNA and regulates gene expression

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28
Q

Compare the speed in which binding of a hydrophilic or hydrophobic ligand takes effect

A

Hydrophilic:
Relatively fast as it relies on ion channels and enzyme action

Hydrophobic:
This action is relatively slow compared to extracellular receptors as they are dependent on transcription and translation

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29
Q

What is meant by ‘amplification’ of cellular signals?

Give an example of how this might occur

A

A cell taking a small stimulus and creating a large effect

For example:
By stimulating the action of an enzyme the binding of a chemical signalling molecule to a single receptor can cause the modification of hundreds or thousands of substrate molecules

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30
Q

Give 2 examples of how responses to different receptors can affect heart rate

A

Increased heart rate:

  • Noradrenaline binds to Beta1 adrenoceptors in cardiac pacemaker cells
  • This leads to increased heart rate

Decreased heart rate:

  • Ach binds to M2 muscarinic receptors in cardiac pacemaker cells
  • This leads to a decrease in heart rate
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31
Q

Give 2 examples of how responses to different receptors can affect glycogen metabolism

A

Breakdown:
Insulin binds to receptors in hepatocytes and increases glycogen breakdown

Synthesis:
Glucagon binds to receptors in hepatocytes and increases glycogen synthesis

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32
Q

Where does phagocytosis occur in mammals?

A

Only found in specialised cells

i.e. Macrophages and neutrophils

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33
Q

Describe the process of phagocytosis

A

Binding of a particles that is recognised by receptors in the plasma membrane

The cell extends pseudopods (fingerlike tendrils of plasma membrane) that permit further receptor interactions with the particle

Particle is internalised via a ‘membrane zipping’ process

Lysosomes fuse forming a phagolysosome in which the particulate is degraded

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34
Q

What is phagocytosis used for?

A

Permits the clearance of damaged cellular material and invading organisms for destruction

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35
Q

What is pinocytosis?

What is it used for?

A

Invagination of the plasma membrane to form a lipid vesicle

This permits the uptake of impermeable extracellular solutes and retrieval of plasma membrane

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36
Q

What are the two forms of pinocytosis?

A

Fluid phase

Receptor mediated endocytosis (RME)

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37
Q

What feature of LDLs allows their uptake into cells via receptor mediated endocytosis (RME)?

A

Apoprotein B on the LDL’s surface bind to LDL receptors on cells (that specifically recognise ApoB)

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38
Q

What cells might synthesise and express LDL receptors on their surface?

A

Cells that require cholesterol

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39
Q

Where are LDL receptors found on the cell surface?

What percentage of the total cell surface does this include?

A

Localised in clusters in clathrin coated pits

CCPs cover about 2% of the cell surface

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40
Q

How do clathrin covered pits form?

A

Form spontaneously, just as clathrin spontaneously forms cages

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41
Q

Describe how LDLs enter a cell and are eventually metabolised

Include the fate of the receptor

A

LDL binds to LDL-R in a clathrin coated pit, the CCP invaginates to form a coated vesicle

Coated vesicle is uncoated in an ATP dependent process, this allows them to fuse with endosomes (larger smooth vesicles)

Ph of the endosome is lower than the cytoplasm (5.5-6.0) which reduces the LDL-R affinity for LDL and so they dissociate

Receptors are sequestered to a domain within the endosome which buds off and returns them to the cell surface (maybe via the golgi)

Endosomes containing LDL fuse with lysosomes and the cholesterol is hydrolysed from esters and released into the cell

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42
Q

What is another name for an endosome?

A

CURL

Compartment for the Uncoupling of Receptor and Ligand

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43
Q

Why is receptor mediated endocytosis useful?

A

Specific binding of molecules to cell surface receptors permits the selective uptake of substances

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44
Q

Describe the structure of the clathrin coat

A

Clathrin (180kDa) and 2 light chains (35kDa) associate to form a three legged structure called a triskelion

It is proposed that triskelions associate to form a basket-like structure consisting of hexagons and pentagons

Attaches to the membrane via integral membrane adapter proteins

Integral proteins associate with both clathrin and receptors, hence locating receptors in the pit

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45
Q

What mutations in the LDL receptors have been identified?

What condition do these mutations contribute to/cause?

A

Mutations causing receptor deficiency

Mutations causing non-functional receptors (normal coated pits and internalisation)

Mutations in which receptor binding is normal:

  • No internalisation due to a C-terminal deletion which prevents LDL-R association with coated pits
  • LDL-Rs then spread over the cell surface

These mutations found in people with hypercholesterolaemia

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46
Q

Describe how Fe3+ is taken up by cells

Include the fate of the receptor

A

Taken up by receptor mediated endocytosis

Two Fe3+ ions bind to apoptransferrin to form transferrin

Transferrin binds to transferrin receptors (in the coated pits) at neutral pH and is internalised

The clathrin pit invaginates and forms a coated vesicle, which is uncoated in an ATP dependent process

The vesicle fuses to an endosome

Upon reaching the acidic endosome, the Fe3+ dissociates from transferrin, however at this pH apoptransferrin remains associated with the receptor

The complex is sorted in the endosome and returned to the cell surface, where apoptransferrin dissociates in the neutral pH

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47
Q

Describe how insulin is taken up by cells

Include the fate of the receptor

A

Insulin receptors begin scattered over the cell surface

Insulin receptors only congregate over coated pits when bound to an agonist (due to binding resulting in a conformational change that makes the receptor recognisable to the pits

The pit invaginates and forms a coated vesicle which is uncoated in an ATP dependent process

Vesicle fuses with an endosome

Receptor and insulin remain bound even at low pH and the entire complex is targetted to lysosomes for degradation

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48
Q

Explain how insulin uptake into the cell leads to insulin desensitisation

A

Receptors are not recycled, so binding of insulin reduces receptor number on the cell

So when circulating insulin levels are high the cell becomes desensitised

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49
Q

Explain the process of transcytosis

A

Uptake of ligand-receptor complexes via receptor mediated endocytosis (clathrin pits, vesicles, endosome etc)

Receptor-ligand complex remains bound in the endosome and is directed to a transport vesicle that shuttles it out of the cell

50
Q

Give an example of transcytosis

A

IgA is taken up by receptor mediated endocytosis and transported to the bile in the liver

In this case, IgA receptors are cleaved during transport resulting in the release of an Ig with a bound secretory component that directs it to the bile

51
Q

4 forms of receptor mediated endocytosis exist, what are the similarities between the forms?

A

Binding of ligand and receptor occurs in the clathrin pits

Pathway from clathrin pits to the endosome is common to all types

52
Q

What is the major difference between the 4 types of receptor mediated endocytosis?

A

Destination of the receptor and ligand

53
Q

How are receptors that have undergone receptor mediated endocytosis targeted to their locations?

Where does the sorting of receptors by destination occur and how do the receptors reach their destinations?

A

Short amino acid motifs

Sorting occurs in CURL (endosome)

Sorted to discreet regions of membrane that bud off to form transport vesicles

54
Q

For each form of receptor mediated endocytosis give:

  • The fate of the receptor
  • The fate of the ligand
  • Example(s) of ligand(s) that are taken up
  • Their general function

You might want to cover the answers with your hand for this card and give the answers to each type one by one, then uncover that type. This does assume you can recite them in the order we were taught them.

A

Type 1:

  • Recycled
  • Degraded
  • LDLs
  • Metabolite uptake

Type 2:

  • Recycled
  • Recycled
  • Transferrin
  • Metabolite uptake

Type 3:

  • Degraded
  • Degraded
  • Insulin, Immune complexes
  • Receptor down-regulation, removal of foreign antigens

Type 4:

  • Transported
  • Transported
  • IgA, Maternal IgG
  • Transfer of large metabolites across a cell
55
Q

How does receptor mediated endocytosis contribute to the development of type 2 diabetes

What form of RME is involved?

A

Constant high levels of insulin result in insulin receptor down-regulation and the tissues become insulin resistant

This only results in more insulin being produced and more down-regulation, leading to the development of T2 diabetes

Mode 3 RME

56
Q

Describe how membrane enveloped viruses and some toxins can gain entry to the cell via receptor mediated endocytosis

A

Exploit endocytotic pathways by adventitious binding to receptors on the plasma membrane

Once inside the endosome the acidic pH allows viruses to fuse with the endosomal membrane

This allows the release of viral RNA into the cell where it can be translated and replicated by the host cell machinery

57
Q

Give 2 examples of toxins which use receptor mediated endocytosis to gain entry to a cell

What receptor do they bind to?

A

Cholera toxin and diphtheria toxin

GM1 ganglioside

58
Q

What are the 4 classes of synapse that Ach acts at?

A

Parasympathetic pre ganglionic
Parasympathetic post ganglionic
Sympathetic pre ganglionic
Sympathetic post ganglionic exceptions

59
Q

What is Ach synthesised from and where?

A

Synthesised from choline and acetylCoA

At the axon terminals

60
Q

How is Ach package for release?

A

Packaged into vesicles at the axon terminals

An energy dependent pump acidifies the vesicle and then vesicular Ach transporter (VAchT) is used to exchange protons for Ach

61
Q

Outline how Ach is released from the nerve cell

A

Action potential reaches the axon terminal, calcium ions enter the cell

Calcium binds to synaptotagmin, causing the vesicle to be brought to the membrane

Snare complex forms a fusion pore through which Ach is released into the synaptic cleft

62
Q

Give an example of an agent that might interfere with Ach release

A

Botulinum toxin

63
Q

What happens to Ach once released into the synaptic cleft?

A

Binds to receptors on the post synaptic cell membrane

Acetylcholinesterase degrades Ach, forming choline and acetate

These products are reabsorbed by the presynaptic neurone and will be recycled

64
Q

Briefly list some sites of parasympathetic innervation and the what effect parasympathetic stimulation will have

A

Salivary glands:
- Produce watery, high enzyme saliva

Heart:
- Decreased heart rate and conduction velocity

Stomach:
- Promotes digestion

Bladder:
- Promotes urination

Penis:
- Erection

Descending colon:
- Peristalsis

65
Q

There are two forms of Ach receptor, for each form give the:

  • Name of the form
  • Receptor type
  • Another agonist specific to that form
  • An antagonist
A

Nicotinic Ach receptor (NAchR):

  • Ligand gated ion channel (Cations)
  • Nicotine is an agonist
  • Scopolamine

Muscarinic Ach receptor:

  • G-protein coupled receptor
  • Muscarine is an agonist
  • Atropine
66
Q

Explain how each Ach receptor type got its name

A

Muscarinic Ach receptors bind to muscarine (agonist)

Nicotinic Ach receptors bind to nicotine (agonist)

67
Q

Which type of Ach receptor subtype can be found at the ganglionic junction?

A

Nicotinic Ach receptor

68
Q

Explain how binding of Ach to Nicotinic receptors leads to an action potential being generated in the postsynaptic neurone

A

2 Ach molecules bind

Pore opens and Na+ floods into the cell K+ out of the cell

This causes depolarisation of the membrane as Na+ predominates

Vm reaches threshold and voltage gated Na+ channels open, leading to an action potential

69
Q

Where might you find muscarinic Ach receptors?

A

Parasympathetic neuroeffector junctions

70
Q

What are the different types of muscarinic Ach receptors?

A

M1 - M5

M1 to M3 are the focus of the course content

71
Q

For the 3 important subtypes of muscarinic Ach receptor, give:

  • The G-protein is is coupled with
  • The effector
  • Whether it activates or inhibits that effector
A

M1:

  • Gq
  • Activates phospholipase C

M2:

  • Gi
  • Inhibits adenlyl cyclase

M3:

  • Gq
  • Activates phospholipase C
72
Q

Briefly describe the series of events the couple activation of M2 muscarinic Ach receptors to the effector

A

M2 activation at the SAN and AVN leads to uncoupling from Gi protein

Gi proteins inhibit adenlyl cyclase hence reducing intracellular levels of cAMP

This leads to reduced heart rate

73
Q

What type of Ach receptor is present in the:

  • SA node
  • Bronchi
  • Bladder
  • Glands

For each tissue, give the receptor subtype and action

A

Parasympathetic muscarinic

SA node:

  • M2
  • Decresed AP frequency

Bronchi:

  • M3
  • Bronchoconstriction

Bladder:

  • M3
  • Contraction of detrusor muscles (urination)

Glands:

  • M1
  • Secretion
74
Q

What do cholinoceptor agonists do?

What is the benefit of a cholinoceptor agonist specific to one receptor subtype?

A

Mimic some or all of the actions of Ach

Specific agonists can be used to elicit a more specific response

75
Q

Give an example of a specific cholinoceptor agonist and its actions

A

PIlocarpine or cevimeline are selective M3 agonists

Increase salivation and lacrimal secretions

76
Q

What are cholinoceptor antagonists used for and why are they used for these reasons?

A

GI disorders because they:

  • Cause hypermobility of GI tract
  • Facilitate endoscopy
  • Anti-spasmodic
  • Treat peptic ulcers

Premedication before general anaesthesia, because:

  • They calm the patient
  • Dry up secretions
77
Q

What are some of the side effects of cholinoceptor antagonists?

A 
Drowsiness
Constipation
Urinary retention
Dry mouth
Blurred vision
Tachycardia
78
Q

What is Glaucoma?

A

Increased aqueous humour that leads to increased ocular pressure

This reduces blood flow to the retinal cells and optic nerve, this can result in blindness

79
Q

What can cause glaucoma?

A 
Diet
Ethnicity (East asian, inuit and african)
Sex (women more likely)
Genetics
Steroid use
Diabetic retinopathy
Trauma
80
Q

How might increasing parasympathetic tone in the eye slow the progression of glaucoma?

A

Increases cilliary contraction, this leads to drainage of fluid and decrease in interocular pressure

81
Q

Which receptor is targeted clinically in glaucoma treatment?

What ligand (drug) is used and what does it do?

A

M3

Pilocarpine:

  • Decreased fluid production by the cilliary bodies
  • Increase drainage to relieve pressure
82
Q

What is the effect of sympathetic innervation in the eye?

A
  • Increases aqueous humour production by the cilliary bodies
  • Increases pressure in the eye
  • Causes dilation of the pupil
83
Q

What agents can be used to help treat glaucoma that are active at adrenoceptors?

What are their effects?

A

Adrenergic receptor antagonists:

  • Decrease sympathetic tone and
  • Decrease humour production from ciliary bodies
  • Increase drainage
  • Decrease cilliary blood supply
84
Q

Where is noradrenaline the major neurotransmitter?

A

Post ganglionic neuroeffector junctions of sympathetic fibres

85
Q

How is noradrenaline synthesised?

A

From tyrosine

Converted to DOPA by tyrosine hydroxylase

DOPA converted to Dopamine by Aromatic amine decarboxylase

Dopamine converted to Noradrenaline by Dopamine Beta-hydroxylase

NB: Noradrenaline then converted to adrenaline by phenylethanolamine-N-methytransferase

86
Q

Are there any other neurotransmitters (apart from NA) involved at sympathetic neuroeffect junctions?

A

Dopamine

87
Q

What is the difference between dopaminergic and noradrenergic neuroeffector junctions?

A

Dopaminergic:

  • Enzyme Dopamine Beta-hydroxylase is not expressed
  • Dopamine released

Noradrenergic:

  • Dopamine Beta-hydroxylase expressed
  • NA synthesised from dopamine
  • NA released
88
Q

How is NA packaged for release?

A

Dopamine is packaged into synaptic vesicles

Dopamine then converted to NA by DBH

Vesicles then ready for release

89
Q

Describe what happens to NA after it is released from the presynaptic neurone

A

Crosses the synaptic cleft and binds to adrenergic receptor on post synaptic neurone and produces an effect

Activity ceases upon reuptake into the neurone or it is inactivated by enzymes

90
Q

What are some important sites of sympathetic innervation?

Include action of sympathetic stimulation at these sites

A

Heart (increased heart rate)

Skin (sweating)

Capillaries (vasoconstriction)

Lungs (bronchodilation)

91
Q

How does NA increase heart rate?

A

Activates B1 adrenoceptors in SAN

Increases cAMP

SAN produces increased frequency of APs

Thus increased heart rate

92
Q

How does NA increase contractile force of the heart?

A

Activates B1 receptors

Increase in cAMP leading to:

  • Increased Ca2+ entry during AP
  • Increased uptake of Ca2+ into sarcoplasmic reticulum

This increases sensitivity of contractile proteins to Ca2+

Thus increases force of contraction

93
Q

What are the 4 types of adrenoceptor?

What type of receptors are they?

A

Alpha1
Alpha2
Beta1
Beta2

G-protein coupled

94
Q

What G protein is each adrenoceptor type coupled to?

What effects do these G proteins have on what effectors?

A

A1:

  • Gq
  • Stimulates Phospholipase C

A2:

  • Gi
  • Inhibits Adenylyl cyclase

B1 and B2:

  • Gs
  • Stimulate Adenylyl cyclase
95
Q

By what mechanism(s) is NA cleared from the synaptic cleft?

A

Mechanism 1:

  • Re-uptake of NA into presynaptic neurone for re-use
  • 80%

Mechanism 2:
- Monoamine oxidase and catechol-O-methyltransferase (MAO and COMT) degrade NA into vanillylmandelic acids

96
Q

How can NA be useful in assessing adrenal medulla function?

A

Vanillylmandelic acids (Metabolite of NA) can be detected in urine and used to determine adrenal medulla activity and hence sympathetic nervous system activity

97
Q

What effects does NA have on the liver

Include the receptor subtype for each effect

A

A1 and A2:

- Increase glycogenolysis

98
Q

What effects does NA have on the Vascular smooth muscle?

Include the receptor subtype for each effect

A

A1:
- Vasoconstriction

B2:
Vasodilation

99
Q

What effects does NA have on the smooth muscle of the GI tract?

Include the receptor subtype for each effect

A

A1:
- Contraction

A2 and B2:
- Relaxation (Increased motility)

100
Q

What effects does NA have on the smooth muscle of the airways?

Include the receptor subtype for each effect

A

B2:

- Bronchodilation

101
Q

What effects does NA have on the smooth muscle of the bladder?

Include the receptor subtype for each effect

A

A1:
- Contraction

B2:
- Relaxation (predominant)

102
Q

What effects does NA have on the SAN and AVN?

Include the receptor subtype for each effect

A

B1:

  • SAN = Increased heart rate
  • AVN = Increased conduction velocity
103
Q

What effects does NA have on the ventricles of the heart?

Include the receptor subtype for each effect

A

B1:

- Increased force of contraction

104
Q

What effects does NA have on adipose tissue

Include the receptor subtype for each effect

A

A1:
- Increased glycogenolysis and gluconeogenesis

B2:
- Increased lipolysis and thermogenesis

105
Q

What effects does NA have on skeletal muscle?

Include the receptor subtype for each effect

A

B2:

- Increased glycogenolysis, thermogensis (shivering) and anabolism

106
Q

What effects does NA have on the Iris?

Include the receptor subtype for each effect

A

A1:

- Dilate pupils

107
Q

What effect does adrenalin have on adrenergic receptors?

A

Non-specific, non-dominant agonist

108
Q

What is the advantage to stimulating specific subtypes of adrenergic receptors rather than all of them?

A

Specific, localised effects

Minimal side effects

109
Q

What drug is used to reverse bronchoconstriction in asthmatics and what receptor subtype is it an agonist for?

A

Salbutamol

Adrenergic B2

110
Q

What drug is used to aid decongestion of the nasal passages and what receptor subtype is it an agonist for?

A

Oxymetazoline or Phenylephrine

Adrenergic A1

111
Q

What drug is used to prolong the effects of local anaesthesia and what receptor subtype is it an agonist for?

A

Adrenaline

Adrenergic A1

112
Q

List two adrenergic antagonists and give:

  • Their clinical uses
  • The receptor subtype they’re an antagonist for
  • One unwanted side effect
A

Prazosin:

  • Treating hypertension and anxiety
  • Alpha
  • Orthostatic hypotension

Propanolol:

  • Treating angina pectoris, bronchospasms
  • Beta
  • Insomnia
113
Q

What 3 compounds can inhibit NA synthesis?

A

Alpha methyltyrosine
Alpha methylDOPA
Guanethidine

114
Q

What enzyme is inhibited by alpha methyltyrosine?

What condition is aMT used to treat?

A

Tyrosine hydroxylase

Pheochromocytoma

115
Q

How does alpha methylDOPA inhibit NA synthesis?

A

Acts as a competitive inhibitor for DBH (false substrate)

Is converted to alpha methyladrenaline and alpha methylnoradrenaline, these accumulate in axon terminals

116
Q

What is alpha methylDOPA used to treat and why?

A

Treats hypertension

Stimulates Alpha adrenergic receptors in the brain

117
Q

What is guanethidine?

How does guanethidine inhibit sympathetic activity?

A

A sympathetic neurone blocker

Inhibits NA release and causes depletion of NA

118
Q

What is guanethidine used to treat?

How does it work?

A

Hypertension:

- prevents vasoconstriction and decreases cardiac output

119
Q

Why is guanethidine no longer used clinically?

A

Side effects:

  • Postural hypotension
  • Delayed ejaculation
  • Increased GI motility and Diarrhoea
  • Sodium and water retention
120
Q

Why are adrenoceptor agonists and antagonists the preferred tools for inhibiting noradrenergic action?

A

They mimic the action of body chemicals, enhancing or preventing effects

They work by modulating natural systems

ESA2 Callum's Cards - Complete (36 decks)

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