Receptors Flashcards
(31 cards)
define a drug
any chemical substance which when administered by a living organism produces a biological effect
define drug effect
either physiological or psychological, usually the interaction between the drug and the body or effect arising from the conscious belief of the drug
compare and contrast LGIC and GPCRs
comparison:
both have TM domains
contrast:
LGIC have pore in the membrane, they produce a fast response and have 3,4,5 TM domains
GPCRs have no pore in the membrane and they produce a secondary cascade, they also produce a slower response
give example for LGIC 3,4,5 TM receptors
3 - P2X receptor
4 - NMDA receptor
5 - nicotinic ACh receptor
describe how a nicotinic receptor is activated and its structure
5 TM domain, 2 alpha, 1 beta, 1 gamma, 1 delta unit
2 ACh must bind for the channel to open
causes an influx of Na+ which activated signalling pathway
name an inhibitor for neurotransmission
atracurium
describe the mechanism of GPCRs
7 TM signal when ligand binds
G protein is activated
dissociation of G alpha subunit to activate or inhibit effector dependent on the pathway
effectors trigger response such as ion channels or enzymes
give a clinical example for LGIC acting drug
atracurium
neuromuscular blocker used for tracheal intubation and muscle relaxation for mechanical ventilation at the nicotinic receptor
competes with ACh
give a clinical example for GPCR acting drug
doxazosin
lowers blood pressure
alpha blocker for post-synaptic receptors
define kinase
a protein or enzymes which can alter the function of another protein from the addition of a phosphate
describe the structure of kinase linked receptors, name the two types and their differences
extracellular N-terminal ligand binding
transmembrane alpha helix
intracellular terminus
cytokine receptor, the tyrosine residue is not bound to the structure
growth factor receptor, the tyrosine residue is bound to the structure
describe the structure of nuclear receptors (inc classes)
monomeric proteins
bound to heat shock proteins
4 classes - steroid, lipid, dimeric orphan and monomeric orphan
tertiary structure which is usually soluble ligand activating transcription factors
describe the mechanism of action for kinase linked receptors and protein phosphorylation
ligand binds
receptor dimerization
conformational change
kinase activation
receptor transphosphorylation
phospho tyrosines for signalling proteins bind to kinase
phosphorylation of kinase cascade (RAD, Mek, Erk phosphorylated)
binds to transcription factor to initiate gene transcription
describe the mechanism of action of class 1 nuclear receptors
ligand passes both membranes
binds to receptor in cytosol
releases heat shock proteins (HSP90 acts as chaperone to keep ligand from binding)
receptors homodimerize
translocation to the nucleus to bind to hormone response elements on DNA
recruits co activator proteins and RNA polymerase to regulate gene transcription
up regulate or down regulate
describe the mechanism of action of class 2 nuclear receptors
ligand passes both membranes
binds to nucleus
releases repressors
heterodimerises with retinoid X receptor
RNA polymerase regulates gene transcription
up regulates only
name the two sites of drug targets for kinase linked receptors
target ligand binding site
inhibit kinase
name a clinical use of which a drug that affects nuclear receptors
tamoxifen
treats breast cancer
competitive against ER (most breast cancers are ER-positive) which blocks the effects of oestrogen
inhibits growth of breast cancer cell and its survival
describe the neurotransmitters and corresponding receptors involved in ANT (note exceptions)
sympathetic - uses ACh at nicotinic to activate the receptor, as a response will release noradrenaline
the noradrenaline will stimulate adrenergic receptors (alpha and beta 1,2,3)
parasympathetic - uses ACh as neurotransmitter
end organ receptors are muscarinic
when ACh binds ACh is released to the end organ
exceptions - sweat glands and adrenal medulla due to acting more like ganglia, they use ACh and nor noradrenaline, adrenal medulla will release adrenaline upon stimulation and sweat glands release ACh
potential sites of action for drugs on the ANS and name some drug examples
conducted AP - tetrodotoxin
neurotransmitter synthesis - botox
neurotransmitter release - botox
neurotransmitter disposition - physostigmine
postsynaptic neurone -pyridostigmine
target organ function
define structure activity relationship
the relationship between the chemical structure and the 3D structure of a molecule relative to its biological activity
captopril
ACE inhibitor - prevents conversion from angiotensin 1 to angiotensin 2
binding sites include
coordinate bind between Zn+ and negative charge
hydrogen bond on NH group
ionic interaction between COO- and NH3+ on the enzyme
antihistamine
inverse agonist
when histamien binds it promotes an active open structure
when antihistamine binds it promotes the inactive closed structure
name the types of muscarinic receptors
M1, M3, M5 - Gq coupled
M2, M4 - Gi coupled
what are muscarinic receptors activated by?
muscarine
causes overstimulation which produces symptoms such as epigastric pain, vomiting, diarrhoea, salivation, diaphoresis
