Intracellular Signalling (session 2) Flashcards
What is signal transduction?
Transmission of molecular signals from a cell’s exterior to its interior
What are the three superfamilies of cell surface receptor?
G protein-coupled (7TM (transmembrane)) receptors
Ligand-gated (receptor operated) ion channels
Receptors with intrinsic enzymatic activity (heterogenous receptor)
What are GPCR agonists?
Bind to receptor and activate it, leading to intracellular signal transduction events. Have affinity and efficacy
What are GPCR antagonists?
Bind to receptor but do not activate it (block effects of agonists at receptor). Have affinity but no efficacy
What is an example of a GPCR agonist?
Salbutamol and analgesia/anaesthesia
What is an example of GPCR antagonist?
Cardiovascular and neuroleptics (anti-schizophrenic)
What do different GPCRs respond to?
Ions (H+ and Ca2+)
Neurotransmitters (ACh, glutamate)
Peptide and non-peptide hormones (glucagon and adrenaline)
Large glycoproteins (thyroid-stimulating hormone)
What is the common basic structure shared by all GPCRs?
Single polypeptide chain (300-1200AAs), also called serpentine 7-TM spanning regions Extracellular N terminal Intracellular C terminal Varying size of N and C
How do GPCRs cause change in cellular activity?
~Activated GPCR must interact with G protein
~GPCR-G protein (guanine nucleotide exchange factor (GEF)) interaction activates G protein by causing GTP to exchange for GDP on G protein alpha subunit-GTP replaces GDP because high conc of GTP in cells
~alpha-beta/gamma complex dissociates and each interact with effector proteins
~GTPase hydrolyses GTP back to GDP and alpha-GTP an beta/gamma subunits reform
What are the subunits that G proteins are made of?
Alpha
Beta
Gamma
(Structurally trimeric but functionally dimeric so alpha and beta/gamma)
Name effectors that are also enzymes
Adenylyl cyclase
Phospholipase C
PI3K
cGMP phosphodiesterase
Name effectors that are ion channels
Voltage-operated Ca2+ channels (VOCCs)
G protein-regulated inwardly-rectifying K+ channels (GIRKs)
Which reaction does adenylyl cyclase catalyse?
ATP -> cyclic AMP
Which reaction does phospholipase C catalyse?
PIP2 -> IP3 + DAG (diacyl glycerol)
Define inotropy
Force with which heart contracts
What is positive inotropy?
Blood-borne adrenaline and sympathetically released noradrenaline interact with ventricular beta1-adrenoceptors to increase force of contraction
In the CNS and PNS, what modulates neurotransmitter release?
Presynaptic GPCRs
Why does the “receptor -> G protein -> effector” reaction happen on the plasma membrane?
It concentrates all the components on the same domain.
Which Gs coupled receptors stimulate adenylyl cyclase? (3)
Beta-adrenoceptors
D1 dopamine receptors
H2 histamine receptors
Which Gi coupled receptors inhibit adenylyl cyclase?
Alpha2-adrenoceptors
D2 dopamine receptors
Mu opioid receptors
What do the R and C subunits of cAMP do?
R=regulates the C subunit
C=catalytic subunit, phosphorylates target proteins in the cell
What effect does IP3R activation have on cytoplasmic [Ca2+]?
Increases [Ca2+] by 5-10 fold (from 1 x 10-7 M) within a few seconds of agonist addition
Which Gq coupled receptors stimulate phospholipase C?
Alpha1-adrenoceptors
M1 muscarinic receptors
H1 histamine receptors
