L14 - What Is A Receptor: Types And Functions Flashcards
What are the main protein targets for drug action?
- receptors
- ion channels
- enzymes
- transporters
What are ion channels?
Allow passage of channel-specific ions down a conc grad
- open in response to environmental cue
- present on membranes
What are the types of drugs that act on ion channels?
- blockers
- modulators
What do blockers do at ion channels? Eg?
Blocks channel - prevents ion movement
- lidocaine, blocks VG Na+ channels
What do modulators do at ion channels?
Increases/decreases chance of channel opening
- gabapentin - reduces activity of VG Ca+ channels
What do enzymes mediate? And act as?
- mediate biochemical signals within cells and tissue
- act as biological catalyst accelerating chemical reactions
What are the types of drugs that act on enzymes?
- inhibitors
- false substrates
- prodrug
What are transporters (carrier proteins)?
Transport substances across membranes against a conc grad (active transport)
- doesn’t open to both sides, actively moves substance
What type of drugs that act on transporters?
- inhibitors
- false substrates
What do inhibitors do at transporters? Eg?
Block the transport of substances
- fluoxetine, serotonin transport blocker
What do false substrates do at transporters?
Abnormal compound accumulates
- amphetamine, acts on dopamine and noradenaline transporters
What do inhibitors do at enzymes? Eg?
Prevents activity
- aspirin, cycloozygenase inhibitor
What do false substrates do at enzymes? Eg?
Abnormal metabolite produced
- fluorouracil, chemotherapy
What do prodrugs do at enzymes? Eg?
Activation of drug molecule
- codeine, converts to morphine
What are receptors?
Proteins that respond to exogenous cue and realy signal into a cell to produce a response
- allow fine tuning of physiological function
What type of drugs act on receptors?
- agonist
- antagonist
- modulator
What do agonists do at receptors? Eg?
Activate the receptor
- morphine, activates opioid receptors
What do antagonists do at receptors? Eg?
Block the receptor, endogenous activators unable to bind
- naloxone, blocks opioid receptors
What do modulators do at receptors? Eg?
Increases/decreases receptor activation
- diazepam, enhances GABA receptor activation
What is the definition of a ligand?
Something that binds
(Doesn’t imply any activity)
What is the definition of an agonist?
Something that binds and produces a response
What is the definition of an antagonist?
Somethings that binds and produces no response
What is the definition of second messenger?
Relay signal from receptor to effector within cells
What is the definition of a signal transduction?
Sequence of second messengers that elicit a biological response
Basics of ligans-receptor interactions:
- ligand binds to receptor = conformational change of receptor protein
- cellular effect (opening of channel, activation of linked enzyme, recruitment of effector protein, intracellular transport)
(Signal - action - response)
What are the 4 main families of receptors?
- ligand gated ion channels
- g protein coupled receptors
- kinase linked receptors
- nuclear receptors
What are ligand gated ion channels? Eg?
Channels that open in response to ligand binding
- allwos movement of channel-specific ions
- Ach and NAch receptors
What are the steps in Ach and Nicotinic receptors?
- electrical impulse travels down pre-synaptic neuron
- triggers release of Ach
- Ach acts on nAChRs on post-synaptic neuron
= opens channels, influx of Na+ = impulse
What is kinase? What does it act as?
- enzyme - phosphorylates target
- acts as swicth
- turns target on/off
- allows other 2nd mes to bind
What are receptors like in kinase-linked receptors? What happens?
- two halves in the membrane (monomer)
- ligand-receptor engagements bring two together (dimer)
= activates kinase activity of receptor
= downstream cascade/biological response
Eg of kinase linked factor:
Epidermal growth factor receptor (EGFR)
- promotes cell growth
- more EGFR = more growth
What are G protein coupled receptors? What happens?
Receptor with 7 transmembrane domains, coupled to G protein
- ligand binding activates G proteins = interacts with effector
What are the steps in GPCR activation?
- resting state
- ligand binds, GDP -> GTP
- GTP bound G protein interacts with effector = biological response
- GTP hydrolysed, G protein dissociates from effector
Eg for GPCR:
Muscarinic M3 GPCRs (on intestinal smooth muscle)
- activation = contraction (peristalsis)
- antimuscarins used for IBS
What are nuclear receptors? What happens?
Receptor not associated with cell membrane
- ligand enters cells, bind to receptor in cytoplasm
- ligand-receptor complex moves to nucleus
= acts on gene expression
Eg for nuclear receptors:
Oestrogen receptor
- important for sexual maturation, gestation
- more oestrogen receptors = more growth = cancer
- susceptible to targeted therapy (tamoxifen)
