Introduction to Pharmacology Flashcards
What are the four types of receptors?
Ligand-gated ion channels, G-protein coupled receptors, kinase-linked receptors and nuclear receptors.
What is the difference between endogenous and exogenous ligands?
Endogenous ligands are made within the body, exogenous ligands come from an external source.
True or false? Antagonists activate receptors.
False. Agonists activate receptors.
How do antagonists work?
Antagonists block an agonist ligand from binding to the receptor, preventing response BUT having no effect on the receptor itself.
What is the difference between the functional site and the binding site?
The functional site is where the response to the ligand binding to the cell is produced. The binding site is where the ligand binds to the cell.
Define specific ligand.
Specific ligands bind to only one type of receptor.
Define selective ligand.
Selective ligands can bind to more than one type of receptor. This is because of similarities in the molecular structure of ligands.
What is the potency of an agonist?
The amount of an agonist required to induce a response, expressed as a dose or a concentration.
Does a high potency agonist require a higher or lower dose than a low potency agonist to induce an effect?
A high potency agonist requires a lower dose to induce an effect.
What is the affinity of a ligand?
How well the ligand binds to a receptor.
What is the efficacy of a ligand?
How effective a ligand is in activating a response. This only applies to agonists (because antagonists only block the binding of agonists, they do not activate responses themselves).
The effect a ligand has on a cell is proportional to the number of …………occupied.
Receptors.
Is the binding of endogenous agents and drugs to receptors reversible?
Yes. The exception is poisons!
What three bonds / interactions determine the strength of ligand-receptor reactions? What type of bond is NEVER involved in ligand-receptor reactions?
- Electrical charge interactions.
- Hydrogen bonding.
- Hydrophobic interactions.
Ligand-receptor reactions NEVER involve covalent bonding.
Receptors follow the law of mass action, which states…
…‘the rate of a chemical reaction is proportional to the product of concentrations of reactants’.
Concentation of drug + concentration of receptor = concentration of drug/receptor complex.
What is the difference between acute drug treatment and chronic drug treatment?
Acute drug treatment is a single treatment which induces an immediate response, due to direct action of the drug on a receptor.
Chronic drug treatment is repeated treatment that induces a delayed response due to indirect action on a receptor.
What is a free agonist?
An agonist that is not bound to a receptor.
Why can chronic drug treatment lead to tolerance?
Homeostasis acts to try an minimise the effect of the drug on cells.
Agonists - receptor downregulation / receptor desensitisation.
Antagonists - receptor upregulation / receptor supersensitivity.
How fast do ligand-gated ion channels mediate transmission? And where?
Very fast transmission. In the nervous system, between neurons or at neuromuscular junctions.
What are the ions that travel in and out of cells via ion channels?
K+, Na+, Ca+ and Cl-.
What does cation-specific and anion-specific refer to, in terms of ion channels?
Cation-specific ion channels are only for positively charged ions. Anion-specific ion channels are only for negatively charged ions.
Ionotropic receptors is another term for what?
Ligand-gated ion channels.
Metabotropic receptors is another term for what?
G-protein coupled receptors.
Which is the most abundant receptor type in the body?
G-protein coupled receptors.
How fast are transmissions mediated by g-protein coupled receptors? Where do they take place?
Fast synaptic transmissions.
When an agonist binds to a g-protein coupled receptor, does the receptor induce a response directly?
No. The response is induced indirectly through the g-protein. The receptor itself does not have any functional activity.
The GPCR is a single protein. How many transmembrane domains does it have? What are these domains made up of?
Seven transmembrane domains made up of alpha-helices.
The GPCR has extracellular and intracellular domains - which is n-terminal and which is c-terminal.
Extracellular - n-terminal.
Intracellular - c-terminal.
Which agonists bind to the extracellular loops of g-protein coupled receptors?
Larger agonists, e.g. peptides.
Where on g-protein coupled receptors do smaller agonists (e.g. noradrenaline) bind?
Membrane.
Which loop of the receptor couples it to the g-protein? What do the proteins in the membrane do?
The long, third loop of the receptor couples it to the g-protein. The proteins in the membrane are involved in signal transduction.
Why is the g-protein coupled receptor’s functional response slower than, for example, ligand-gated ion channels?
The intermediate step of coupling the g-protein to the receptor slows down the functional response.
Which proteins are:
Associated with guanine nucleotides GDP and GTP.
Anchored to the internal membrane by lipids.
Trimeric in structure with alpha, beta and gamma subunits.
G-proteins.
In the resting state, g-protein subunits are attached to the membrane as an alpha-beta-gamma complex associated with the receptor. GDP is bound to the alpha subunit. What happens when an agonist binds to this receptor?
The GDP on the alpha-subunit is converted to GTP. The alpha-beta-gamma complex dissociates, resulting in an alpha-GTP and a beta-gamma complex. Both of these are active forms of g-protein which can bind to various effectors in the membrane.
When GPCR is activated and alpha-GTP binds to an effector, GPCR inactivation is triggered. Describe this process.
The binding of alpha-GTP to the effector activates GTPase in the alpha-subunit, converting alpha-GTP to alpha-GDP. Alpha-GDP reforms with the beta-gamma subunit to reform the alpha-beta-gamma complex again, which reassociates with a receptor in the membrane. The complex is ready for reactivation.
These secondary messenger systems,, which can have various effects in the cell, are targeted by…?
Adenylyl cyclase.
Phospholipase C.
Ion channels.
G-proteins.
How do kinase-linked receptors mediate communication? Is this fast or slow?
Kinase-linked receptors mediate slow (seconds-hours) communication by altering gene transcription.
What targets kinase-linked receptors?
Various peptides (e.g. cytokines, growth factors) and hormone (e.g. inulin). These are involved in various functions, e.g. cell growth, cell differentiation, immune reponse etc.
What is a kinase?
An enzyme which phosphorylates (adds a phosphate group to) the amino acid group of a protein.
What is an enzyme which phosphorylates the amino acid group of a protein?
Kinase.
What is the function of a phosphatase?
Dephosphorylating (removing a phosphate group from) proteins.
Phosphorylation is a mechanism by which ………….. ………….. ………… can be controlled.
Secondary messenger proteins.
Name the FOUR types of kinase-linked receptors.
HINT: it depends on the amino acid being phosphorylated.
- Tyrosine kinases.
- Serine/threonine kinases.
- Cytokine kinases.
- Guanylyl cyclase-linked receptors.
What does the kinase-linked receptor tyrosine kinase do?
Phosphorylates tyrosine.
What does the kinase-linked receptor serine/threonine kinase do?
Phosphorylates serine/threonine.
What activates the kinase-linked receptor cytokine kinase?
Cytokines.
What do guanylyl cyclase-linkedmkinase receptors do?
Form cGMP.
Describe the process whereby a kinase-linked receptor is activated when a ligand binds.
When a ligand binds, two receptors associate in the membrane, forming a dimer.
This dimerisation causes the autophosphorylation of intracellular tyrosine.
The phosphorylated tyrosine residues serve as intracellular binding sites for other secondary messenger proteins.
What effect do the increased number of intermediate steps in kinase-linked receptors (when compared with GPCR and ligand-gated ion channels) have on the speed of the functional response?
It is much slower!
How do nuclear receptors mediate communication? How fast or slow is this?
Nuclear receptors alter gene transcription to mediate very, very slow (hours-days) responses.
What are the targets of nuclear receptors?
Why is this important?
Various hormones (e.g. steroids, thyroid hormones) and fat-soluble vitamins (vitamin A, vitamin D).
This is important for endocrine function and drug metabolism.
Why are many nuclear receptors known as ‘orphan receptors’?
We know that the receptor exists, but teh endogenous ligand has not been discovered.
True or false? Nuclear receptors are NOT located on the plasma membrane.
True.
Why don’t nuclear receptors need to be located on the membrane?
HINT: their ligands are lipid-soluble…
Their ligands are lipd-soluble, so they can pass straight through the membrane.
There are Class I and Class II nuclear receptors. Where is each located?
Class I - cytosol.
Class II - nucleus.
One type of nuclear receptor forms homodimers when activated, the other forms heterodimers. Which is which?
Class I - homodimers.
Class II - heterodimers.
Where do all nuclear receptors act to alter gene expression, regardless of whether they are Class I or Class II?
In the nucleus.
Which class of nuclear receptor includes steroid (e.g. oestrogen, progesterone) receptors?
Class I.
Which class of nuclear receptors bind lipid ligands (e.g. fatty acids, cholesterol)?
Class II.
Nuclear receptors have ………………. domains in a single …………………. chain.
Four, polypeptide.
Name the four domains of nuclear receptors.
- N-terminal domain.
- DNA binding domain.
- Hinge region.
- Ligand binding domain.
Which of the nuclear receptor domains contains the co-activator region to bind to transcription factors?
N-terminal domain.
Which of the nuclear receptor domains has cysteine-rich zinc fingers, which are linked to zinc ions. They bind to DNA to alter gene transcription?
DNA binding domain.
Which region of the nuclear receptor is the binding site for the two nuclear receptors in dimerisation?
Hinge region.
Which domain of the nuclear receptor is where a specific ligand binds to the different receptors?
Ligand binding domain.
Acetylcholine can act on which TWO types of receptors?
Ligand-gated ion channels and g-protein coupled receptors.
What is this process?:
‘molecular mechanisms involved in translating signal induced by receptor binding into functional response in the cell.’
Signal transduction.
Kinase-linked receptors have a large ………………… ligand-binding domain and an ……………………. catalytic domain of variable size.
Extracellular, intracellular.
In the activation of kinase-linked receptors, the phosphorylation of tyrosine residue acts as a catalyst for…?
…another protein to come in.
