Pharmacology: Receptors and Signalling Flashcards
what is autocrine signalling
cell signals to itself
what is paracrine signalling
cell signals to its close neighbours
what is endocrine signalling
blood vessels transport cell’s signalling molecules to distant target cells
what are the 4 main types of receptors
- LGICs
- GPCRs
- kinase-limited receptors
- nuclear receptors
where are LGICs and what are their ligands
- plasma membrane
- hydrophilic signalling molecules, ‘fast’ neurotransmitters
where are GPCRs and what are their ligands
- plasma membrane
- hydrophilic signalling molecules, ‘slow’ neurotransmitters
where are kinase-limited receptors and what are their ligands
- plasma membrane
- hydrophilic protein mediators
where are nuclear receptors and what are their ligands
- intracellular, cytoplams or nucleur membrane
- hydrophobic signalling molecules
what are the 3 things that a ion channel may be gated by
- transmembreane voltage (VGICs)
- chemical signals (ligand)
- physical stimuli (mechanical energy, temp)
what do ion channels do
create a ion conducting transmembrane pore
what do LGICs consist of
several subunits creating a central ion-conducting channel
what can LGICs do
rapidly alter membrane potential
describe what happens when an agonist binds to a LGIC
agonist binds -> rapid conformational change -> ion channel opens -> ions conducted down electrochemical gradient -> cycles back to closed state
what are secondary messenger system
receptor activation modulates an effectors activity
may increase or decrease rate of synthesis of secondary messenger molecules
basic structure of a G protein
- peripheral membrane protein
- 3 subunits - alpha, beta and gamma
- alpha subunit has a binding site for GDP/GTP
describe the difference between an active/inactive G protein
- active, alpha subunit binds to GTP and dissociated from beta and gamma subunits (alpha-bound GTP and beta/gamme dimer)
- inactive, alpha subunit binds to GDP
describe what happens during GPCR activation
- agonist binds and a conformational change occurs which:
- alpha released GDP, allowing GTP to bind
- alpha dissociates and regulates the effectors activity
- agonist can dissociate but signalling can persist
describe what happens when GPCR dissociates
- the alpha subunit acts as an enzyme hydrolysing GTP to GDP + Pi
- signal is turned off
- alpha recombines with the beta and gamma subunits
- G protein cycle complete
describe GPCR signalling via adenyl cyclase and cAMP and pkA
- G protein activated, Gs + GTP binds and activates adenyl cyclase
- this converts ATP to cAMP
- cAMP activate pkA, causing residue phosphorylation
- cellular effects
- G protein activated, Gi + GTP inhibits adenyl cyclase
describe GPCR signalling via PLC, pkC, IP3, Ca2+ and DAG
- G protein activated, Gq and GTP bind to phospholipase
- PLC converts PIP2 to IP3 releasing DAG
- IP3 binds to IP3 receptor in the ER, this releases Ca2+ causing cellular effects
- DAG binds to pkC, causing phosphorylation of residues and finally cellular effects
describe signalling via protein kinases
- agonist binds and activated protein kinase
- this causes autophosphorylation of residues
- multiple adaptor proteins are recruited in response and phosphorylated
- cellular effects
what is another name for nuclear receptors
ligand-gated transcription factors
describe signalling via nuclear receptors
- steroid hormones enter the cell via diffusion and bind to the IC receptor
- inhibitory protein dissociates and the steroid receptor moves to the nucleus
- this forms a dimer and binds to the hormone response elements in DNA
- transcription is switched on/off, altering mRNA levels and rate of synthesis of mediator proteins
