M&R S6 - Receptors and Membrane Turnover + Presentation Content (S7 included) Flashcards
How are chemical signals classified?
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
What is a ligand?
Any small molecule that binds specifically to a receptor site
What are the two major types of ligand and what are their functions? (broadest terms)
Agonists:
Activates receptors
Antagonist:
Binds without causing activation of receptor
What is a receptor?
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
How are receptors classified?
According to the agonist that they recognise
Sub classification can be made on the basis of their affinity to a series of antagonists
What is the difference between a receptor and an acceptor?
An receptor is always functionally silent when unbound
A ‘receptor’ that operates in the absence of its ligand is an acceptor
What is meant by ‘signal transduction’?
When a ligand binds to a receptor (the signal) a physiological response is generated
(signal results in action - transduction)
How is signal transduction performed with hydrophobic and hydrophillic molecules?
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
What governs the responsiveness of a cell to a signalling molecule?
Presence of absence of a specific receptor
What similarities are there between enzymes and receptors?
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
What are the differences between receptors and enzymes?
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
Give some examples of processes that receptors are involved in
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
What are some common mechanisms by which extracellular hydrophilic signals are transduced into a cellular event
Membrane bound receptors with integral ion channels
Membrane bound receptors with integral enzyme activity
Membrane bound receptors which couple to effectors via transducing proteins
Describe the general action of membrane bound receptors with integral ions channels
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
What are the two types of membrane bound receptor with integral ion channels (ligand gated ions channels)?
Classical
Non-classical
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
Pentameric subunits
4 transmembrane domains
Nicitonic Ach receptors (nAchR)
Give an example of a non-classical membrane bound receptor with integral ion channel
Ryanodine receptors (Ca2+)
Describe the general action of membrane bound receptors with integral enzyme activity
Give some examples of such receptors
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
Describe how tyrosine kinase linked receptors initiate cellular response to the binding of a ligand
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
What is another name for membrane bound receptors with transducing proteins?
G-protein coupled receptors
OR
Seven transmembrane domain receptors
Describe the structure of a membrane bound receptor with transducing proteins (GPCR)
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
How do G-protein coupled receptors operate?
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
Give some examples of membrane bound receptors with transducing proteins
Muscarinic Ach receptors
Dopamine receptors
5-HT receptors
Light, smell and taste receptors
How does the action of G-proteins on an effector vary and what effect does this have?
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
Give some examples of hydrophobic ligands
Steroids (Cortisol, oestrogen, testosterone)
Thyroid hormones
How do intracellular receptors appear in their resting state?
Bound to heat shock or chaperone proteins
Describe what happens when an intracellular receptor is activated
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
Compare the speed in which binding of a hydrophilic or hydrophobic ligand takes effect
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
What is meant by ‘amplification’ of cellular signals?
Give an example of how this might occur
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
Give 2 examples of how responses to different receptors can affect heart rate
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
Give 2 examples of how responses to different receptors can affect glycogen metabolism
Breakdown:
Insulin binds to receptors in hepatocytes and increases glycogen breakdown
Synthesis:
Glucagon binds to receptors in hepatocytes and increases glycogen synthesis
Where does phagocytosis occur in mammals?
Only found in specialised cells
i.e. Macrophages and neutrophils
Describe the process of phagocytosis
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
What is phagocytosis used for?
Permits the clearance of damaged cellular material and invading organisms for destruction
What is pinocytosis?
What is it used for?
Invagination of the plasma membrane to form a lipid vesicle
This permits the uptake of impermeable extracellular solutes and retrieval of plasma membrane
What are the two forms of pinocytosis?
Fluid phase
Receptor mediated endocytosis (RME)
What feature of LDLs allows their uptake into cells via receptor mediated endocytosis (RME)?
Apoprotein B on the LDL’s surface bind to LDL receptors on cells (that specifically recognise ApoB)
What cells might synthesise and express LDL receptors on their surface?
Cells that require cholesterol
Where are LDL receptors found on the cell surface?
What percentage of the total cell surface does this include?
Localised in clusters in clathrin coated pits
CCPs cover about 2% of the cell surface
How do clathrin covered pits form?
Form spontaneously, just as clathrin spontaneously forms cages
Describe how LDLs enter a cell and are eventually metabolised
Include the fate of the receptor
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
What is another name for an endosome?
CURL
Compartment for the Uncoupling of Receptor and Ligand
Why is receptor mediated endocytosis useful?
Specific binding of molecules to cell surface receptors permits the selective uptake of substances
Describe the structure of the clathrin coat
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
What mutations in the LDL receptors have been identified?
What condition do these mutations contribute to/cause?
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
Describe how Fe3+ is taken up by cells
Include the fate of the receptor
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
Describe how insulin is taken up by cells
Include the fate of the receptor
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
Explain how insulin uptake into the cell leads to insulin desensitisation
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
Explain the process of transcytosis
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
Give an example of transcytosis
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
4 forms of receptor mediated endocytosis exist, what are the similarities between the forms?
Binding of ligand and receptor occurs in the clathrin pits
Pathway from clathrin pits to the endosome is common to all types
What is the major difference between the 4 types of receptor mediated endocytosis?
Destination of the receptor and ligand
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?
Short amino acid motifs
Sorting occurs in CURL (endosome)
Sorted to discreet regions of membrane that bud off to form transport vesicles
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.
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
How does receptor mediated endocytosis contribute to the development of type 2 diabetes
What form of RME is involved?
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
Describe how membrane enveloped viruses and some toxins can gain entry to the cell via receptor mediated endocytosis
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
Give 2 examples of toxins which use receptor mediated endocytosis to gain entry to a cell
What receptor do they bind to?
Cholera toxin and diphtheria toxin
GM1 ganglioside
What are the 4 classes of synapse that Ach acts at?
Parasympathetic pre ganglionic
Parasympathetic post ganglionic
Sympathetic pre ganglionic
Sympathetic post ganglionic exceptions
What is Ach synthesised from and where?
Synthesised from choline and acetylCoA
At the axon terminals
How is Ach package for release?
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
Outline how Ach is released from the nerve cell
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
Give an example of an agent that might interfere with Ach release
Botulinum toxin
What happens to Ach once released into the synaptic cleft?
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
Briefly list some sites of parasympathetic innervation and the what effect parasympathetic stimulation will have
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
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
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
Explain how each Ach receptor type got its name
Muscarinic Ach receptors bind to muscarine (agonist)
Nicotinic Ach receptors bind to nicotine (agonist)
Which type of Ach receptor subtype can be found at the ganglionic junction?
Nicotinic Ach receptor
Explain how binding of Ach to Nicotinic receptors leads to an action potential being generated in the postsynaptic neurone
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
Where might you find muscarinic Ach receptors?
Parasympathetic neuroeffector junctions
What are the different types of muscarinic Ach receptors?
M1 - M5
M1 to M3 are the focus of the course content
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
M1:
- Gq
- Activates phospholipase C
M2:
- Gi
- Inhibits adenlyl cyclase
M3:
- Gq
- Activates phospholipase C
Briefly describe the series of events the couple activation of M2 muscarinic Ach receptors to the effector
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
What type of Ach receptor is present in the:
- SA node
- Bronchi
- Bladder
- Glands
For each tissue, give the receptor subtype and action
Parasympathetic muscarinic
SA node:
- M2
- Decresed AP frequency
Bronchi:
- M3
- Bronchoconstriction
Bladder:
- M3
- Contraction of detrusor muscles (urination)
Glands:
- M1
- Secretion
What do cholinoceptor agonists do?
What is the benefit of a cholinoceptor agonist specific to one receptor subtype?
Mimic some or all of the actions of Ach
Specific agonists can be used to elicit a more specific response
Give an example of a specific cholinoceptor agonist and its actions
PIlocarpine or cevimeline are selective M3 agonists
Increase salivation and lacrimal secretions
What are cholinoceptor antagonists used for and why are they used for these reasons?
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
What are some of the side effects of cholinoceptor antagonists?
Drowsiness Constipation Urinary retention Dry mouth Blurred vision Tachycardia
What is Glaucoma?
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
What can cause glaucoma?
Diet Ethnicity (East asian, inuit and african) Sex (women more likely) Genetics Steroid use Diabetic retinopathy Trauma
How might increasing parasympathetic tone in the eye slow the progression of glaucoma?
Increases cilliary contraction, this leads to drainage of fluid and decrease in interocular pressure
Which receptor is targeted clinically in glaucoma treatment?
What ligand (drug) is used and what does it do?
M3
Pilocarpine:
- Decreased fluid production by the cilliary bodies
- Increase drainage to relieve pressure
What is the effect of sympathetic innervation in the eye?
- Increases aqueous humour production by the cilliary bodies
- Increases pressure in the eye
- Causes dilation of the pupil
What agents can be used to help treat glaucoma that are active at adrenoceptors?
What are their effects?
Adrenergic receptor antagonists:
- Decrease sympathetic tone and
- Decrease humour production from ciliary bodies
- Increase drainage
- Decrease cilliary blood supply
Where is noradrenaline the major neurotransmitter?
Post ganglionic neuroeffector junctions of sympathetic fibres
How is noradrenaline synthesised?
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
Are there any other neurotransmitters (apart from NA) involved at sympathetic neuroeffect junctions?
Dopamine
What is the difference between dopaminergic and noradrenergic neuroeffector junctions?
Dopaminergic:
- Enzyme Dopamine Beta-hydroxylase is not expressed
- Dopamine released
Noradrenergic:
- Dopamine Beta-hydroxylase expressed
- NA synthesised from dopamine
- NA released
How is NA packaged for release?
Dopamine is packaged into synaptic vesicles
Dopamine then converted to NA by DBH
Vesicles then ready for release
Describe what happens to NA after it is released from the presynaptic neurone
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
What are some important sites of sympathetic innervation?
Include action of sympathetic stimulation at these sites
Heart (increased heart rate)
Skin (sweating)
Capillaries (vasoconstriction)
Lungs (bronchodilation)
How does NA increase heart rate?
Activates B1 adrenoceptors in SAN
Increases cAMP
SAN produces increased frequency of APs
Thus increased heart rate
How does NA increase contractile force of the heart?
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
What are the 4 types of adrenoceptor?
What type of receptors are they?
Alpha1
Alpha2
Beta1
Beta2
G-protein coupled
What G protein is each adrenoceptor type coupled to?
What effects do these G proteins have on what effectors?
A1:
- Gq
- Stimulates Phospholipase C
A2:
- Gi
- Inhibits Adenylyl cyclase
B1 and B2:
- Gs
- Stimulate Adenylyl cyclase
By what mechanism(s) is NA cleared from the synaptic cleft?
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
How can NA be useful in assessing adrenal medulla function?
Vanillylmandelic acids (Metabolite of NA) can be detected in urine and used to determine adrenal medulla activity and hence sympathetic nervous system activity
What effects does NA have on the liver
Include the receptor subtype for each effect
A1 and A2:
- Increase glycogenolysis
What effects does NA have on the Vascular smooth muscle?
Include the receptor subtype for each effect
A1:
- Vasoconstriction
B2:
Vasodilation
What effects does NA have on the smooth muscle of the GI tract?
Include the receptor subtype for each effect
A1:
- Contraction
A2 and B2:
- Relaxation (Increased motility)
What effects does NA have on the smooth muscle of the airways?
Include the receptor subtype for each effect
B2:
- Bronchodilation
What effects does NA have on the smooth muscle of the bladder?
Include the receptor subtype for each effect
A1:
- Contraction
B2:
- Relaxation (predominant)
What effects does NA have on the SAN and AVN?
Include the receptor subtype for each effect
B1:
- SAN = Increased heart rate
- AVN = Increased conduction velocity
What effects does NA have on the ventricles of the heart?
Include the receptor subtype for each effect
B1:
- Increased force of contraction
What effects does NA have on adipose tissue
Include the receptor subtype for each effect
A1:
- Increased glycogenolysis and gluconeogenesis
B2:
- Increased lipolysis and thermogenesis
What effects does NA have on skeletal muscle?
Include the receptor subtype for each effect
B2:
- Increased glycogenolysis, thermogensis (shivering) and anabolism
What effects does NA have on the Iris?
Include the receptor subtype for each effect
A1:
- Dilate pupils
What effect does adrenalin have on adrenergic receptors?
Non-specific, non-dominant agonist
What is the advantage to stimulating specific subtypes of adrenergic receptors rather than all of them?
Specific, localised effects
Minimal side effects
What drug is used to reverse bronchoconstriction in asthmatics and what receptor subtype is it an agonist for?
Salbutamol
Adrenergic B2
What drug is used to aid decongestion of the nasal passages and what receptor subtype is it an agonist for?
Oxymetazoline or Phenylephrine
Adrenergic A1
What drug is used to prolong the effects of local anaesthesia and what receptor subtype is it an agonist for?
Adrenaline
Adrenergic A1
List two adrenergic antagonists and give:
- Their clinical uses
- The receptor subtype they’re an antagonist for
- One unwanted side effect
Prazosin:
- Treating hypertension and anxiety
- Alpha
- Orthostatic hypotension
Propanolol:
- Treating angina pectoris, bronchospasms
- Beta
- Insomnia
What 3 compounds can inhibit NA synthesis?
Alpha methyltyrosine
Alpha methylDOPA
Guanethidine
What enzyme is inhibited by alpha methyltyrosine?
What condition is aMT used to treat?
Tyrosine hydroxylase
Pheochromocytoma
How does alpha methylDOPA inhibit NA synthesis?
Acts as a competitive inhibitor for DBH (false substrate)
Is converted to alpha methyladrenaline and alpha methylnoradrenaline, these accumulate in axon terminals
What is alpha methylDOPA used to treat and why?
Treats hypertension
Stimulates Alpha adrenergic receptors in the brain
What is guanethidine?
How does guanethidine inhibit sympathetic activity?
A sympathetic neurone blocker
Inhibits NA release and causes depletion of NA
What is guanethidine used to treat?
How does it work?
Hypertension:
- prevents vasoconstriction and decreases cardiac output
Why is guanethidine no longer used clinically?
Side effects:
- Postural hypotension
- Delayed ejaculation
- Increased GI motility and Diarrhoea
- Sodium and water retention
Why are adrenoceptor agonists and antagonists the preferred tools for inhibiting noradrenergic action?
They mimic the action of body chemicals, enhancing or preventing effects
They work by modulating natural systems
