L5 - secondary messengers Flashcards
why is signal amplification useful?
can provide very sensitive responses to a small amount of primary messenger (efficient)
what does having multiple secondary messenger pathways allow
- more complexity of signalling (and more efficient from a small amt of primary messenger) and graded responses
- allows ligand to produce different responses by acting on different receptors
- allows ligand to produce different effects when acting on the same ligand, but in different areas
give example where the same ligand acting on different receptors causes different effects
NA acting on B2 causes relaxation
NA acting on a1 of smooth muscle causes contraction
give an example where the same ligand acting on the same receptor in different locations causes different effects
ACh acting on M3 in smooth muscle causes contraction
ACh acting on M3 on endothelial cells causes relaxation
what are the features of second messenegrs that allow sensitivity and selectivity of a response
sensitivity -> signal amplification
selectivity -> temporal and spatial localisation
list some common secondary messengers
cAMP and cGMP
IP3, DAG
NO,CO
Ca2+
what effect does Gs activation have on adenylate cyclase action
increases its activity increasing cAMP production
what effect does Gi have on adenylyl cyclase
decreases its activity, decreasing the cAMP production
what effect does Gq/11 have on its secondary messenger?
increases IP3 and DAG production by phospholipase C
what enzyme produces IP3 and DAG, and from what substrate?
phospholipase C
PIP2 substrate
how do all 3 plasma membrane receptor types
GPCRs
LGICs
Tyrosine kinase linked receptors (intrinsic enzymes)
affect 2ndary messenger activity
GPCR G proteins alter the activity of enzymes and production levels of 2ndary messengers
LGICs alter ion entry (specifically Ca)
TKLRs phosphorylate and activate enzymes/protein kinases
describe phosphorylation process
- kinases target serine/threonine/tyrosine residues in proteins and phosphorylate them (adding phosphate group to their hydroxyl group)
- the phosphate group is negatively charged and so can cause conformational changed based on surrounding charges
- this can alter protein activity
what is signal amplification? define
taking a small starting signal eg 1x NT and making it a much bigger signal
‘activation of one receptor by one extracellular transmitter induces synthesis of multiple 2nd messengers and alters the activity of multiple targets’
how does signal amplification occur?
- increasing the no. of active molecules at each stage of a cascade
- using multiple pathways
Describe a signal amplification pathway and describe it
- 1x NA acts on GPCR and activate 1 adenylate cyclase
- 1x adenylate cyclase can make many cAMP molecules
- 2x cAMP can activate a PKA
- each activated PKA can phosphorylate many targets
what is BDNF? where is it synthesised and where does it end up
Brain Derived Neurotrophic factor
synthesised in primary sensory neurones and is transported to terminals
where does BDNF bind?
to trkB receptors on spinal/peripheral neurones and glia
what effect does BDNF have when it binds to trkB receptors
alters pain processing (sensitises pain pathways)
how does BDNF binding to trkB receptors alter pain processing?
- alters gene expression (eg increasing expression of Neuropeptides - NTs in dorsal horn)
- increases NMDA receptor acitvation and trafficking to cell surface (enhancing glutamate sensitivity)