signalling, receptors and pharmacology Flashcards
how does aspirin exhibit its biological effect?
irreversibly inhibits cycooxygenase
what is the ligand for the enzyme/receptor cyclooxygenase?
arachidonic acid
how do ligand-gated ion channels exert their effect as a receptor? give an example of one
allow the influx/efflux of ions in order to cause depolarisation/hyperpolarisation to bring about a cellular response
nicotinic acetylcholine receptors
how do most receptors with intrinsic enzymatic activity exert their effect as receptor? give an example of one
often cause phosphorylation of key amino acids, leading to gene transcription and production of proteins which exert a cellular effect
insulin receptor
how do intracellular receptors differ from most of the subtypes of receptors? name an intracellular receptor
they can cross the cell membrane
glucocorticoid receptors
give 2 examples of EXOGENOUS adrenoceptor ligands
isoprenaline
salbutamol
what is meant by the statement ‘isoprenaline is a subtype selective adrenoceptor ligand’?
acts upon only a few of the 9 adrenoceptors, producing a selective response
give an example of an exogenous adrenoceptor antagonist
propranolol
what is meant by the lock-and-key concept when referring to receptors?
the points of hydrophobic, electrostatic and ionic interactions within the flexible 3D landscape of the receptor binding pocket
how does a ligand-receptor complex form?
the receptor protein transitions between multiple different conformations and the ligand stabilises a particular conformation which brings about a cellular response
what forces is ligand binding governed by?
kinetics of association and dissociation
what does Emax refer to?
the maximum cellular response to a ligand
what is EC50? how can it be found from graphical data?
the effective concentration of ligand producing 50% of Emax
the midpoint of a sigmoidal curve
how can radioligand binding be used to quantify drug-receptor binding?
the radioactive form of the agonist/antagonist binds to the cells, allowing equilibrium to form. excess washed off, test
repeat with higher [ligand] until most of the receptor sites are filled
what information does radioligand binding provide?
how many receptors are present
affinity of the ligand for the receptor
define ‘antagonist’
possesses affinity for the receptor but lacks the ability to cause receptor activation and therefore cannot bring about a cellular response
what is the observed difference when a log of an antagonist response is plotted against the log of an agonist response?
right-ward shift in the curve
what is meant by the term ‘signal transduction’?
the way in which a cell allows a response to be generated from an extracellular signal
give an example of a receptor with intrinsic enzymatic activity and explain how it works
epidermal growth factor receptor
EGF binds, activating an enzyme which phosphorylates the enzyme itself and other substrates, triggering the cellular response
give 2 examples of B2-adrenoceptor agonists
salbutamol, salmeterol
give two examples of u-opioid receptor agonists
morphine, fentanyl
give 2 examples of D2- dopamine receptor agonists
haloperidol, sulpiride
what is the general structure of a GPCR?
-single polypeptide chain -7 transmembrane spanning regions -extracellular N-terminal -intracellular C-terminal
which two regions of a GPCR can be responsible for ligand binding?
- binding site formed from 2-3 transmembrane domains
- the N-terminal region
