L15 - what is a receptor: types & function Flashcards
what is pharmacology?
the science of drugs and how they act in a biological system.
drug that acts on effector causes what?
biological response
4 main protein drug targets
- receptors
- ion channels
- enzymes
- transporters
describe ion channels
- proteins that are in plasma membrane
- open in response to environmental cues (e.g memb depol)
- allows channel specific ions to pass DOWN a conc. gradient
(the one that looks like a tunnel)
how can drugs modify ions channels?
via blockers or modulators
what are blockers in ion channels?
drug blocks ion channel so ions can’t pass through
what are modulators in ion channels?
modulators increase or decrease the chance of channel opening
what do enzymes do?
- cause biochemical signals within cells + tissues
- biological catalyst
3 types of enzyme receptors?
- inhibitors
- false substrates
- prodrug
what do enzyme inhibitors do?
prevent activity
what do enzyme false substrates do?
cause abnormal metabolite production (the product produced from substrate is different that what it should be)
what do prodrugs do?
enzymes will activate prodrugs into activate drug molecules
what are transporters/ carriers?
- carries substances across membranes
- move substances AGAINST conc. gradient (via AT)
- diff from channel proteins as not open on both sides
inhibitors in transporters
they block the transport / carrier protein
false substrates in transporters
transporter recognises drug as something it wants to carry but it is not native so the drug has a different action
what are receptors?
- proteins which are on surface of cell membranes
- respond to exogenous cue
- substance binds to receptor to produce a response
- response allows physiological function
3 types of substances for receptors
- agonists
- antagonists
- modulators
agonist
something that activates a receptor
antagonist
binds to receptor but doesn’t produce a response, so blocks receptor so essentially turns receptor off
modulators
drugs that bind else where on receptors. decrease or increase receptor activation
define ligand
something that binds
second messenger
relay signal within a from receptor to effector
signal transduction
sequence of second messengers that elicit biological response
ligand receptor interactions
- ligand binds to receptor
- this causes conformational change of receptor
- leading to a cellular effect
so single causes action which causes response
examples of cellular effects causes by ligand binding to receptor
- channel opens
- activation of linked enzyme
- effector proteins recruited
- intracellular transport
4 types of receptor?
- ligand gated ion channels
- kinase linked receptors
- G protein coupled receptors
- nuclear receptors
describe ligand gated ion channels
- not voltage gated
- channel opens when ligand binds
- allows specific ions to move through
- e.g ACh abd nicotinic acetylcholine receptors
example of ligand gated ions channels: ACh + nicotinic receptors
- electrical impulse travels down pre-synaptic neuron
- triggers release of ACh from vesicles into synaptic cleft
- ACh acts on nAChRs on post synaptic neurone
- opens channel + allows Na+ to enter
- triggering impulse
describe kinase
- second messenger
- enzyme uses ATP to phosphorylate a target
- diff kinases act on diff targets
- turns targets on and off
- allows other second messengers to bind
how do kinase linked receptors work?
- sit on cell membrane as 2 halves
- when ligand binds they come together to form dimer
- dimer is active receptor
- this activates kinase that is fused to the receptor
- kinase phosphorylates target
- causes response
epidermal growth factor receptor (EGFR) and lung cancer
- EGFR is a kinase linked receptor
- it can promote cell growth
- some lung cancers express. ore EGFR proteins causing more growth
- so these cancers are susceptible to drugs that target EGFR
describe G protein coupled receptors
- has 7 transmembrane domains
- coupled to a G protein
- when ligand binds it activates G protein which will interact with effector
- different GPCRs are coupled to diff G proteins so elicit diff responses
describe GPCR activation (nucleotide exchange)
- resting state: GPCR is linked linked to G protein which is bound to GDP (guanasine di phosphate)
- when ligand binds the receptor activates + G protein switches out GDP for GTP
- this activates G protein and this GTP bound G protein associates with target effector to cause a response
- to move back to resting state, G protein will hydrolyse the GTP to make it GDP which makes G protein dissociate from effector
muscarinic receptor and smooth muscle contraction
- GPCR receptor example
- how peristalsis works in intestine
- neurons signal to smooth muscle cells
- ACh released and acts on muscarinic M3 receptors
- this activates G protein Gq
- this causes Ca to enter smooth muscle cells causing contraction
- forcing food through intestine
what are antimuscarinics used for?
for irritable bowel syndrome
nuclear receptors
- associated with cell membrane
- ligand enters cell and binds to receptor in cytoplasm
- ligand receptor complex moves into nucleus
- acts on gene expression
oestrogen receptors and breast cancer
- oestrogen receptor example of hormone nuclear receptor
- important for equal maturation, gestation
- some patients will have cancer cells that express more oestrogen receptors causing uncontrollable cell growth
what are breast cancer patients given?
tamoxifen which targets oestrogen nuclear receptors
