Receptor & G Proteins Flashcards
define a superfamily?
group of receptors having similar bass structures and mechanism of signal transduction
what are the 4 superfamilies?
- G protein-coupled receptors (GPCRs)
- ligand gates ion channels (LGICs)
- tyrosine kinase-linked receptors
- steroid receptors (nuclear receptors)
what are the largest family of cell surface receptors?
GPCRs
what do GPCRs mediate?
cellular responses to big diversity of signalling molecules
inc:
- hormones
- proteins
- neurotransmitters
same ligand can activate many diff fam members to produce effect
what is the location and signal transduction mechanism of the M1 receptor?
nerves
inc IP3, DAG cascade
what is the location and signal transduction mechanism of the M2 receptor?
heart, nerves
dec cAMP prod, activation K+ channels, inhibition Ca2+ channels
what is the location and signal transduction mechanism of the M3 receptor?
glands, smooth muscle, endothelium
inc IP3, DAG cascade
what is the location and signal transduction mechanism of the M4 receptor?
CNS
dec cAMP prod, activation K+ channels
what is the location and signal transduction mechanism of the M5 receptor?
CNS
inc IP3, DAG cascade
where are muscarinic receptors located?
peripheral tissues and CNS
what are the 5 subtypes of muscarinic receptors?
M1, M2, M3, M4, M5
what are M1, M3 and M5 coupled to?
Gq
what are M2 and M4 coupled to?
Gi
what do Gq coupled receptors hydrolyse?
PIP2
what do Gi coupled receptors negatively regulate?
adenylyl cyclase + decrease cAMP production
where are M1, M3 and M4 located and what do they mediate?
cerebral cortex + hippocampus
mediate effects of ACh on learning + memory
what do M1 and M4 occur in and what can they also mediate?
striatum
cholinergic signalling in extrapyramidal motor circuits
where is M2 concentrated in and what does it act as?
basal forebrain
autoreceptors to control ACh synthesis + release
what is the location, structure and signal transduction mechanism of the Nm receptor?
skeletal neuromuscular junction
pentameric (2-alpha-beta-delta-gamma)
Na+ depolarising ion channel
what is the location, structure and signal transduction mechanism of the Nn receptor?
post-synaptic cell bodies, dendrites
alpha + beta subunits only usually as 2-alpha-3beta
Na+ depolarising ion channel
where are nicotinic receptors located?
NMJ , autonomic ganglia, CNS
what superfamily are the nicotinic receptors part of?
LGIC
what does the activation of nicotinic receptors lead to?
influx of Na+ ions
how many subunits are nicotinic receptors composed of?
5
where are the alpha1 and beta1 subunits located?
muscle
what stoichiometry ratio are neuronal nACHR’s composed of (alpha to beta)?
2:3
what can homomeric receptors (alpha7) form?
a channel
alpha-adrenoreceptors
alpha1 (alpha1A, alpha1B, alpha1D)
potency order: NA > Ad
location: post-junctional effector organs
function: smooth muscle contraction
transduction: inc IP3, DAG
agonist: phenylephrine
antagonist: prazosin
alpha-adrenoreceptors
alpha2 (alpha2A, alpha2B, alpha2C)
potency order: Ad > NA
location: pre-synaptic nerve endings, post synaptic brain, blood vessels
function: inhibition transmitter release, dec sympathetic outflow
transduction: dec cAMP (Ca2+)
agonist: clonidine
antagonist: yohimbine
beta-adrenoreceptors
beta1
potency order: Iso > NA > Ad
location: heart, adipose tissue, JG cell kidney
transduction: inc cAMP
agonist: dobutamine
antagonist: atenolol
beta-adrenoreceptors
beta2
potency order: Iso > Ad > NA
location: bronchi, blood vessels, uterus
transduction: inc cAMP
agonist: salbutamol
antagonist: ICI118551
dopamine receptors
D1 - 1 and 5
signal transduction: inc cAMP
effect: post-synaptic inhibition
dopamin receptors
D2 - 2,3,4,
signal transduction: dec cAMP
effect: pre + post synaptic inhibition, stimulation/inhibition of hormone release
where do GPCRs occur, how do they respond and what does their single polypeptide chain have?
cell membrane
respond in seconds
7-transmembrane helices
what does the tail GPCRs consist of?
serine + threonine residues that = phosphorylated
what does the intracellular loop occur between?
V and VI transmembrane domains
what are the heterotrimeric GTP-binding proteins (G proteins) composed of?
alpha, beta and gamma polypeptide chains
what do both the alpha and gamma subunits have?
lipid molecules that help bind them to plasma membrane
the alpha subunit has … bound
GDP
heterotrimeric GTP binding proteins are ….. and they function as … that can flip between 2 states
GTPases
molecular switches
what are the 2 states?
active when GTP bound
inactive when GDP bound
describe the on and off switching?
- extracellular ligand binds to G protein linked receptor
- receptor changes conformation
- —> rel of GDP + replacement with GTP
- switch turned off when G protein hydrolyses own bound GTP
- converting it back to GDP
the GTP binding causes a conformational change in the surface of alpha subunit
what does this cause the release of?
beta-gamma dimer
allows alpha subunit to interact with target proteins
alpha subunit = GTPase + hydrolyses GTP to GDP
then reassociates with beta-gamma complex
GTPase activity of the alpha subunit is greatly enhanced by binding of second protein called a …
regulator of g-protein signalling (RGS)
what do RGS proteins act as?
alpha subunit specific GTPase activating proteins (GAPs)
play imp role in shutting off g-protein mediated response
Gs protein
alphaS
activates AC (inc cAMP) activates Ca2+ channels
Gi protein
alphaI
inhibits AC (dec cAMP) activates K+ channels
Gq protein
alphaQ
activates PLC-beta turnover (inc Ca2+)
Go protein
alphaO
activates K+ channels
inactivates Ca2+ channels
Gt protein
alphaT
activates cGMP phosphodiesterase in rod photoreceptors
Golf protein
alphaOLF
activates AC in olfactory system
what are the 2 major pathways by which GPCRs generate small intracellular mediators?
- binding of extracellular ligand -> alters conformation of cytoplasmic domain of receptor
- cAMP pathway -> enzyme directly produces cAMP
- enzyme produces inositol triphosphate that rel Ca2+ from ER
