Unit 1 Flashcards
What is the history behind the birth of the receptor concept?
The birth of the receptor concept was the outcome of circumstances in the lives of its two founding fathers, the physiologist John Newport Langley (1852-1925) and the Immunologist and bacteriologist Paul Ehrlich (1854-1915).
John. N. Langley is known as one of the fathers of the chemical receptor theory and as the origin of the concept of ‘receptive substance’ proposed in 1905.
- The concept of specific receptors that bind drugs or transmitter substances onto the cell, thereby either initiating biological effects or inhibiting cellular functions, is today a cornerstone of pharmacological research and pharmaceutical development.
Otto Loewi: Identifying acetylcholine as a neurotransmitter in the parasympathetic nervous system.
Sir Henry Dale: Established the concept of mediators and receptors
Humphrey Rang: Pioneered the study of receptors.
What are drug receptors?
The concept of receptors is central to pharmacology.
“Receptor” is sometimes used to denote any target molecule with which a drug molecule (i.e. a foreign compound rather than an endogenous mediator) has to combine in order to elicit its specific effect.
An important distinction between agonists, which ‘activate’ the receptors, and antagonists, which combine at the same site without causing activation, and block the effect of agonists on that receptor.
What are the four main types of target proteins for drug binding?
- Receptors
- Ion channels
- Enzymes
- Transporters (carrier molecules)
What are agonistic or antagonistic effects on receptors?
Many therapeutically useful drugs act, either as agonists or antagonists, on receptors for known endogenous mediators.
Agonist/inverse agonists:
- Direct: ion channel opening/closing
- Transduction mechanisms:
Enzyme activation/inhibition
Ion channel modulation
DNA transcription
Antagonist:
- No effect
- Endogenous mediators blocked
What are ion channels and blockers vs modulators?
Gateways in cell membranes that selectively allow the passage of particular ions (open or closed)
- Ligand-gated channels
- Voltage-gated channels
Blockers - Permeation is blocked
Modulators - increased or decreased opening probability
What do we know about drugs and enzymes?
- Most drugs are targeted on enzymes.
- Substrate analogue - acts as a competitive inhibitor of the enzyme
- False substrates - inactive product
- Some enzymes act to convert prodrug (inactive form) to an active form
Enzyme inhibitor –> normal reaction inhibited
False substrate –> abnormal metabolite produced
Prodrug –> active drug produced
What are substrate analogues?
Chemical compounds with a chemical structure that resemble the substrate molecule in an enzyme-catalysed chemical reaction
It acts as a competitive inhibitor of the enzyme
What are false substrates?
False substrates are substrate analogues that resemble the substrate closely enough so that an abnormal end product is produced.
What is prodrug?
A biologically inactive compound that can be metabolised in the body by enzymes into an active drug.
What is an enzyme inhibitor?
Molecules that interact with enzymes (temporarily or permanently) in some ways and reduce or prevent enzyme-catalysed reactions.
What are the reactions between inhibitors, false substrates and transporters?
Transporters normally allow movement of ions and small organic molecules across cell membranes.
Inhibitors block the transport either competitively or non-competitively.
False substrates also prevent transport so there is an accumulation of abnormal compound.
What are the four types of receptors?
- Ligand-gated ion channels
- G-protein coupled receptors (GCPRs)
- Kinase-linked and related receptors
- Nuclear receptors
What do we know about Ligand-gated ion channels?
Inc.
- Location
- Effector
- Coupling
- Examples
- Structure
- Ionotropic receptors
- Typically receptors on which fast neurotransmitters act
Control the fastest synaptic events in the nervous system (timescale: millisecond) - Location - Membrane
- Effector - Ion channel
- Coupling - Direct
- Examples - Acetylcholine at the neuromuscular junction or glutamate in the CNS
- Structure - Oligomeric assembly of subunits surrounding central pore.
What do we know about G-protein-coupled receptors (GPCRs)?
Inc.
- Location
- Effector
- Coupling
- Examples
- Structure
- Largest family of receptors
- Metabotropic receptors that are coupled to intracellular effector systems primarily via a G protein
- Receptors for many hormones and slow transmitters, timescale: seconds
- Location - Membrane
- Effector - Channel / enzyme
- Coupling - G protein or arrestin
- Examples - Muscarinic acetylcholine receptor, adrenoceptors
- Structure - monomeric or oligomeric assembly of subunits. Consists of seven membrane-spanning alpha helices, extracellular N-terminal domain and intracellular C-terminal domain, 3rd intracellular loop interacts with the G protein.
What are some main targets for G proteins?
- Adenylyl cyclase, the enzyme responsible for cAMP formation
- Phospholipase C, the enzyme responsible for inositol phosphate (IP) and diacylglycerol (DAG) formation
- Ion channels, particularly calcium and potassium channels
- Rho A/Rho Kinase, a system that regulates the activity of many signalling pathways controlling cell growth, proliferation and smooth muscle contraction
- Mitogen-activated protein kinase (MAP kinase), a system that controls many cell functions, including cell division
What do we know about Kinase-linked receptors?
Inc.
- Location
- Effector
- Coupling
- Examples
- Structure
- Receptor tyrosine kinases (RTKs)
- Receptor serine/threonine kinases
- Cytokine receptors
- Location - Membrane
- Effector - Protein kinases
- Coupling - Direct
- Examples - Insulin, growth factors, cytokine receptors
- Structure - Single transmembrane helix linking extracellular receptor domain to intracellular kinase domain
What do we know about Nuclear receptors?
Inc.
- Location
- Effector
- Coupling
- Examples
- Structure
- Intracellular receptor
- Directly interact with DNA
- Regulate gene transcription
- Two main subfamilies according to their phylogenetic development:
Class I: Located in the cytoplasm; endocrine steroid receptors
Class II: Located within the nucleus; receptors for fatty acid, cholesterol, thyroid hormones etc. - Location - Intracellular
- Effector- Gene transcription
- Coupling - Via DNA
- Examples - Steroid receptors
- Structure - Monomeric structure with receptor- and DNA-binding domains
What are two distinct steps in the generation of the receptor-mediated response by an agonist?
- Binding
- Activation
What is a receptor antagonist?
A receptor antagonist binds to the receptor without causing activation, therefore preventing the agonist from binding.
What is affinity?
The tendency of a drug to bind to the receptors and form a receptor complex
What is efficacy?
The tendency of a drug, once bound, to activate the receptor and evoke a response (the maximum response the drug can produce)
What is potency?
The amount of drug required to produce a defined effect (usually 50% of the maximum)
What do we know about intensity of pharmacological effect?
The intensity of the pharmacological effect is directly proportional to the number of receptors occupied and formation of drug-receptor complex (i.e. rate of association/dissociation)
For most drugs, binding and activation are reversible, dynamic process –> response ceases when this complex dissociates
What is occupancy theory?
The intensity of the pharmacological effect is directly proportional to the number of receptors occupied by the drug.
Maximal response occurs when all the receptors are occupied at equilibrium
Drugs of high potency generally have a high affinity for the receptors and thus occupy a significant proportion of the receptors even at low concentrations.
What are agonists?
Agonists are drugs that mimic natural processes in the body by activating receptors.
What are the three types of agonists?
- Full agonists
- Partial agonists
- Inverse agonists
What is the formula for receptor theory?
D + R ⇌ DR complexes
–> = K+1
<– = K-1
Where D = drug R = receptor
What do concentration-effect and dose-response curves tell us?
Concentration-effect curve (in vitro) and dose response curve (in vivo) allows us to estimate the maximal response that the drug can produce (Emax) and the concentration or dose needed to produce a 50% maximal response (EC50 or ED50)
A logarithmic concentration or dose scale is often used, producing a rectangular hyperbola to sigmoidal curve.
What does a dose-response curve tell us?
Concentration/dose of agonist to produce 50% of maximal response (EC50/ED50) which tells us the relative potencies of drugs
What CAN’T a concentration-response curve tell us?
The affinity of agonists for their receptors
Why is it important to be able to compare drug potency?
- Relevant to drug administration
- Determine the dose required to produce the desired effect
- Generally, the more potent a drug, the more selective it is (i.e. fewer side effects)
What is potency vs efficacy?
Potency is the amount of a drug that is needed to produce a given effect (i.e. EC50/ED50) whereas efficacy is the effect that a drug can produce regardless of dose.
What do we know about spare receptors?
A “maximal response can be produced when only a very small proportion of the total receptors are occupied by a drug.”
Cells have more receptors than required (receptor reserve)
Magnitude of responses is NOT proportional to receptor occupancy
Not all tissues have spare receptors
What is a full agonist vs a partial agonist?
A full agonist produces the maximum possible response
A partial agonist produces a sub-maximal response (no matter how high a concentration is applied, it’s unable to produce maximal activation of the receptors)
How do agonists and partial agonists interact?
Although they are agonists, partial agonists can act as an irreversible competitive antagonist if co-administered with a full agonist.
The partial agonist competes with the full agonist for receptor activation observed with the full agonist alone
What is an inverse agonist?
A drug which produces an effect opposite to that of an agonist (or antagonist), yet acts as the same receptor.
Such compounds have also been described as having negative efficacy.
Constitutively active receptors which exhibit intrinsic or basal activity can have inverse agonists, which not only block the effects of binding agonists but inhibit the basal activity of the receptor:
- A prerequisite for an inverse agonist response is that the receptor must have a constitutive (also known as intrinsic or basal) level of activity in the absence of any ligand
E.g. Antihistamines are inverse agonists of histamine H1 receptors
What do most agonists do?
Mimic natural body processes!
p.s. inverse agonists do not!
What does the size of the response to given concentrations of agonists depend on?
- Concentration at receptors
- Number of receptors available
- Affinity of drug for receptor (potency of drug - assessed as EC50)
- Efficacy of drug/receptor complex (assess as maximum response)
What are the four main types of antagonism?
- Competitive antagonism (interacts with the same binding site as the agonist)
- Reversible
- Irreversible (covalently modify the binding site)
- Non-competitive antagonism (interact with a different site on the receptor to prevent its activation or inhibit an event downstream of the receptor to prevent its activation or inhibit an event downstream of the receptor to prevent the coupling to response)
- Physiological antagonism (activation of a different receptor system with opposite effects to that stimulated by the neurotransmitter or mediator)
What is the other type of antagonism?
Pharmacokinetic antagonism.
“Pharmacokinetics” = the actions of the body on drugs
One drug affecting the absorption, metabolism or excretion of the other
What 4 main things can drugs do?
- Reduce/increase the absorption of another drug
- Increase/decrease the rate at which another drug is metabolised (broken down)
- Increase/decrease the rate at which another drug is excreted
- Displace another drug from plasma protein binding sites
What is an antagonist?
A receptor antagonist is a type of drug that does not provoke a biological response itself upon binding to a receptor but blocks or dampens agonist-mediated responses
An antagonist inhibits the actions of an agonist
What are the clinical uses of antagonists?
To inhibit the actions of endogenous agonists (neurotransmitter or hormone)
To reverse the effects of an agonist that has been administered to a patient
What are the examples of clinical uses of antagonists?
To inhibit the actions of endogenous agonists:
- Excess nasal secretion and itchy eyes in allergic rhinitis (hay fever) can be reduced by loratadine/chlorpheniramine, a histamine receptor agonist.
To reverse the effects of an agonist that has been administered to a patient:
- An overdose of benzodiazepine (sedative) can be reversed by administration of flumazenil, a benzodiazepine receptor agonist
What do antagonists do and what is their affinity and efficacy?
- Bind to target molecules (like receptors)
- Have affinity but no (zero) efficacy
ie. Affinity like an agonist, yet they don’t produce a response, unlike an agonist
The degree of inhibition will depend on the concentration of antagonist administered.
What is the IC50 value?
The inhibitory concentration of antagonist required to inhibit a response by 50%
How is the potency of an antagonist determined?
By its IC50 value
How can the IC50 be calculated for a given antagonist?
By determining the concentration of antagonist needed to elicit half inhibition of the maximum biological response of an agonist.
What does the IC50 value mean?
The lower the IC50, the greater the potency/affinity of the antagonist, and the lower the concentration of drug that is required to inhibit the maximum biological response.
Lower concentrations of drugs may be associated with fewer side effects - at low concentrations drugs are likely to have xd selectivity.
What happens in reversible competitive antagonism?
Bind to receptors at the same binding site as the agonist, but without activating the receptor.
Agonist and antagonist “compete” for the same binding site on the receptor
The receptor can only accommodate one molecule at a time
Once bound, an antagonist will block agonist binding
E.g. Noradrenaline and ß-1 receptor antagonist (i.e. atenolol)
What is the level of activity of the receptor determined by in reversible competitive antagonism?
The relative affinity of each molecule for the site
Their relative concentrations
What is observed in functional assays using reversible competitive antagonists?
A parallel rightward shift of agonist dose-response curves with no alteration of the maximal response is observed.
The extent of the shift being a measure of the dose ratio.
Dose ratio is used to determine the antagonist dissociation constant.
To restore the same level of response (i.e. 100%), a higher concentration of agonist is required to compete with antagonist
How do you find the dose ratio in functional assays using competitive antagonists? What is dose ratio?
The extent of the parallel rightward shift.
Dose ratio is used to determine the antagonist dissociation constant.
What does the schild plot show in reversible competitive antagonism?
The Schild plot is a graphical representation used to determine the antagonist’s affinity for the receptor and its mechanism of action. It typically plots the logarithm of the concentration of the antagonist against the shift in the concentration-response curve induced by the antagonist.
Log(r-1) against log (antagonist concentration)
The X intercept represents the pA2 value for the antagonist (a measure of the potency)
What happens in irreversible competitive antagonism?
Irreversible agonists covalently bind to or alter the receptor target (same site as the agonist) and generally cannot be removed or dissociate very slowly –> inactivating the receptor for the duration
The antagonist effect is determined by the rate of receptor turnover and the rate of synthesis of new receptors
E.g. Phenoxybenzamine, an irreversible alpha blocker - it permanently alkylates alpha-adrenergic receptors, preventing adrenaline and noradrenaline from binding
What is the effect of an irreversible competitive antagonist?
Insurmountable and full agonist occupancy cannot be achieved due to a decrease in available binding sites for agonist.
The antagonist effect is determined by the rate of receptor turnover and the rate of synthesis of new receptors
What is observed in functional assays using irreversible competitive antagonists?
There is both a decrease in slope and a reduction in maximum agonist response
What are non-competitive antagonists?
Non-competitive antagonists, also known as allosteric antagonists, do not compete with agonists at receptors.
They bind to a distinctly separate binding site from the agonist, exerting their action to that receptor via the other binding site.
Blocks at some point downstream from the agonist binding site on the receptor, and interrupts the chain of events that lead to the production of a response by the agonist.
No amount of agonist can completely overcome the inhibition once it has been established (non-surmountable antagonism)
Triamterene and amiloride are non-competitive antagonists of aldosterone by blocking the epithelial sodium channels (ENaC)
What is non-surmountable antagonism?
When no amount of the agonist can completely overcome the inhibition once it has been established.
What is observed in functional assays using non-competitive antagonists?
In the agonist dose-response curves, there is depression of the maximal response.
What is uncompetitive antagonism?
Uncompetitive antagonism is different from non-competitive antagonists in that they require receptor activation by an agonist before they can bind to a separate allosteric binding site.
What is physiological antagonism?
The interaction of two drugs whose opposing actions in the body tend to cancel each other out.
E.g. ß-agonists for obstructive lung disease
EG: Endogenous agonist –> signalling pathway A –> Bronchoconstriction
Exogenous agonist (physiological antagonist) –> Signalling pathway B –> Bronchodilation
Bronchodilation + bronchoconstriction = No overall effect
What is pharmacological tachyphylaxis?
Also known as self-antagonism or desensitisation where repeated administration can decrease an agonist effect.
Many factors can contribute to tachyphylaxis, for example:
- Internalisation of receptors (short-term)
- Down-regulation of signalling pathways
What is the formation of a reversible drug-receptor complex?
A (drug) + R (free receptor) ⇌ AR (complex)
–> = K + 1
<– = K - 1
A = xA (conc of A)
R = Ntot - NA (total receptors - receptors occupied by A)
AR = NA (receptors occupied by A)
k = rate constant
What is the equation for the law of Mass Action?
Rate of forward reaction = K+1xA(Ntot - NA)
Rate of backward reaction = K-1NA
At equilibrium, the two rates are equal =
K+1XA(Ntot - Na) = K-1NA
k = rate constant
A = xA (conc of A)
R = Ntot - NA (total receptors - receptors occupied by A)
AR = NA (receptors occupied by A)
k = rate constant
What is the Equilibrium dissociation constant (KA)?
What is the equation for it?
- A measure of binding affinity between a ligand and its receptor
- The smaller the KA = higher the binding affinity (more tightly bound)
= k-1/k+1 = xA(Ntot - NA)/NA
k = rate constant
xA = conc. of A
Ntot = number of binding sites available
NA = number of binding sites occupied by A
What is occupancy and the equation for it?
Occupancy (PA) is the proportion of receptors occupied
PA = xA / (xA + k-1/ k+1) = xA / xA + kA
PA = (xA / kA) / (xA / kA + 1)
xA = conc. of A
KA = equilibrium dissociation constant
What is the equation for occupancy when more than one drug is present?
Two drugs, A and B, which bind to the same receptor with equilibrium constants KA and KB, are present at concentrations XA and XB
PA = (xA / KA) / (xA / K + xB / Kb + 1)
xA = conc. of A
KA = equilibrium dissociation constant
Adding drug B –> reduces the occupancy by drug A
Right shift without any change of slope or maximum response.
What happens when you add a second drug? (Inc. graph and Schild equation)
Adding a drug (drug B) reduces the occupancy of the other drug (drug A).
There is a right shift without any change of slope or maximum response.
rA represents the extent of the rightward shift, on a log scale, this is known as the Schild equation:
rA = (xB / KB ) + 1 —> log(rA-1) = log xB - logKB
xB = conc. of B
KB = equilibrium constant of B
rA depends on the concentration and equilibrium constant of the competing drug B (not XA or KA)
What characteristics does r show for competitive antagonism?
r shows the following characteristics:
- Depends only on the concentration and equilibrium dissociation constant of the antagonist
- Does not depend on the concentration and equilibrium constant of the agonist
- Increases linearly with xB, and the slope of a plot of (rA - 1) against xB is equal to 1/KB; this relationship, being independent of the characteristics of the agonist, should be the same for an antagonist against all agonists that act on the same population of receptors.
Increasing the dose of any drug does what?
Increases the likelihood of adverse side effects
This is because most drugs are selective but not specific in action
E.g. antihistamines help to reduce allergic reactions but they can cause dry mouth because they block acetylcholine receptors
What does the degree of inhibition caused by a competitive antagonist depend on?
The concentration of the agonist and antagonist
Number of available receptors
Affinity of the antagonist
What are radioligand binding studies?
A radioligand is a radioactively labelled drug that binds to a receptor, transporter, enzyme or any site of interest
Most common method for detecting the receptors in tissue is to use a radioactive drug with high affinity and degree of selectivity
Incubate the tissue with radioactive drug, the radioactive drug (D) will bind to the receptor (R) to form a drug-receptor complex (DR)
D + R ⇌ DR
–> = K + 1
<– = K - 1
The amount of drug-receptor complex (DR) can be measured as it is now radioactive
What are the assumptions with radioligand binding assays?
- All receptors are equally accessible to the radioactive-labelled drug
- Receptors are either free or bound to the radioactive-labelled drug
- Binding does not alter or modify the binding site of the receptors
- Binding is reversible and saturable
- Non-specific non-saturable binding can be subtracted
What are the factors to consider in radioligand binding assays?
Identify an appropriate radioactive ligand/drug for the experiment:
- highly specific,
- high binding affinity,
- high degree of selectivity,
- chemically stable.
A method to separate bound from free ligands:
- Filtration and centrifugation
Way to distinguish specific and non-specific binding:
- Binding to the subtypes of receptors
- Binding to tissue protein
- Binding to objects
How is binding measured in radioligand binding studies?
- Binding is measured in the presence of the highest concentration of radioactive ligand used in a saturation curve
All the receptors would be occupied by radioactive ligands - Binding is also measured in the presence of the same concentration of radioactive ligand and increasing concentrations of unlabelled ligand (inhibitor).
- As the concentration of unlabelled ligand increases
–> radioactive ligand bound decreases (displaced by unlabelled ligand) until a plateau is reached
The residual amount of radioligand represents binding to non-specific, non-saturable sites.
What do we know about radioligand selection and ligand-receptor complexes?
Based on its stability, specific activity and pharmacological selectivity.
In general, antagonists tend to bind to receptors with greater affinity than agonists
- Do not induce conformational changes in ligand-receptor complexes
- Do not activate the receptor, which in some cases if binding with metabolically active cells, can result in desensitisation and reduction in affinity of the receptor.
What are the 3 major types of radioligand study?
- Saturation binding experiments
- Competitive binding experiments
- Kinetics experiments
What happens in a saturation binding experiment?
- Measure equilibrium binding of various concentrations of the radioligands
- Study the relationship between binding and ligand concentration to determine the density of the receptor (Bmax) and ligand affinity (Kd)
What happens in a competitive binding experiment?
- Measure equilibrium binding of a single concentration of radioligand at various concentrations of unlabelled inhibitors
- Study the affinity of the receptor for the competitor which can be used to further characterise the receptor type
What happens in a kinetics experiment?
- Measure binding at various times to determine the rate constants for radioligand association and dissociation
What do we know about the Rosenthal plot in saturation binding experiments?
Analysed the equilibrium data with Rosenthal plot (also known as Scatchard plot)
- Transforms hyperbolical data into linear representation
- Y-axis: Cbound / Cfree
- X-axis: Bound
- Bmax is estimated as x-axis intercept
- Kd is -1 slope
Only valid when the radioligand binds to a single receptor population
What is the purpose of a saturation experiment?
- Determine the affinity (Kd) of a radioligand for a specific receptor
Kd = equilibrium dissociation constant - Determine the density (Bmax) of a specific receptor
Bmax = total number of receptor sites
What are the factors to consider in a saturation experiment?
Concentration of radioligand used:
- At least 6 concentrations equally spaced on either side of the Kd
- Lower concentration approx. 1/10 of the Kd value
- Higher concentration approx. 10x the Kd value
Concentration of tissue used:
- Depends on the number of binding sites (receptors) per milligram of tissue
- Enough tissue needs to be present so that a measurable amount of radioligand is bound at the lowest radioligand concentration
- However, tissue concentration can’t be too high either… ideally no more than 10% of the radioligand is bound.
What is shown in the scatchard plot?
Look at the position of the y-axis intercept to determine whether 10% of the radioligand is bound to the receptor
- Ratio of bound to free ligand should be <0.1
When radioligand is bound to the tissue, the concentration of radioligand decreases
Free = total added - total bound
What is the equation for the saturation curve?
B = Bmax x F / Kd + F
B = bound radioligand
Bmax = total number of receptors
Kd = equilibrium dissociation constant
F = free radioligand
What do we know about determining affinity in competition experiments?
Not all binding sites/receptors have radioligand available for saturation experiments
- Only unlabelled forms are available and therefore unable to directly measure their affinity
However, we can determine the affinity of the unlabelled ligand for the receptor by evaluating its ability to compete with a radioligand
- Various concentrations of unlabelled inhibitors at a single concentration of radioligand for a receptor.
What do we know about the competitive inhibitor, the IC50 and the Ki for competition experiments?
The competitive inhibitor (unlabelled) can be either an agonist or an antagonist, as long as it competes with the radioligand for the receptor.
IC50 = concentration of competing unlabelled ligand which displaces 50% of the specific binding of the radioligand
Ki = inhibition constant of the unlabelled drug
How do you calculate Ki in competition experiments?
Ki = IC50 / 1 + (L / Kd)
IC50 = concentration of competing unlabelled ligand which displaces 50% of the specific binding of the radioligand
Ki = inhibition constant of the unlabelled drug
L = Log (conc. of competing ligand)
Kd = dissociation constant (ligand affinity)
What happens in autoradiography?
- A technique to visualise the anatomical distribution of a protein of interest (i.e. receptor) in tissue by binding a radioligand to its biological target
What happens when quantifying autoradiography?
- Quantification allows for the pharmacological characterisation of ligand affinity by means of dissociation constants (Kd), inhibition constants (Ki) as well as the density of binding sites
- This powerful technique provides information about the localisation and ligand selectivity of the target receptor
What is genome sequencing?
The molecular biology and genetics approach
- Genome-wide identification
- PCR and DNA sequencing
–> Amino acid identification - Understand which receptor proteins are expressed
- No pharmacological information on the response (function)
What do we know about second messenger? (use adrenoceptors as an example)
- Different types of receptor have different second messengers
Using adrenoceptor as an example:
- different families have different second messenger systems
- Alpha 1 receptors: activate phospholipase C, producing inositol triphosphate (IP3) and diacylglycerol (DAG) as second messengers
- Alpha 2 receptors: inhibit adenylyl cyclase –> decreased cAMP
- ß-adrenoceptors: stimulate adenylyl cyclase –> increased cAMP
Part of characterisation of receptor is through the identification of the second messenger system they are coupled to.
What does genetic sequencing tell us?
Provides additional information on the structural properties of the receptor.
How do we characterise receptors?
A combination of different methods is needed
