lecture 05: secondary messengers

how do primary messengers compare to 2ndary in regards to the signal they carry?

primary: carry signals *between* cells (NTs, hormones)

2ndary: carry signals *within* cells AFTER primary signalling

what are 2ndary messengers important for?

* nociception
* proliferation
* neurite outgrowth
* gene expression

how are spatial and temporal localisation of 2nd messengers important for signal specificity (also, consider cascading)?

they relate to the **selectivity of response**

* signal amplification is prod. by increasing number of active signalling molecules @ each stage in a cascade & using multiple pathways

along with spatio-temporal localisation, what else is important for 2ndary signal specificity?

site of production/release AND rate of breakdown/removal

what is signal amplification?

when one receptor is activated by multiple extracellular transmitters; this produces synth of multiple 2ndary messengers to alter activity of **multiple** targets

why is signal amplification useful?

we reduce the amount of extracellular signals & number of receptors req

what is NGF (when is it important, and when is it released)?

this is **neurite growth factor**; it is synth by many diff cells types to stim. organ innervation

* key role in driving neuronal proliferation & survival during NS development
* released during tissue damage & inflammation from epithelial mast cells

how can chronic pain be potentially treated with NGF signalling?

by **blocking NGF signalling**, it can alter pain processing thru __altering gene expression & reducing NaV-activaiton threshold__ to reduce excitability of sensory nerves and prevent binding to trkA receptors on peripheral nerves

what are the 3 major receptor classes involved in 2ndary messengers?

1. GPCRs
2. LGICs
3. TRK-linked receptors

why is phosphorylation so important when considering receptors in 2ndary messaging?

when we phosphorylate proteins, we are changing the shape & thus function of the protein which influences longer-term responses AND the rapid turnover of 2ndary messenger molecules

what are the main types of 2nd messengers?

* cyclic nucleotides
* cAMP
* cGMP
* molecules derived from lipid bilayers
* IP3
* DAG
* arachidonic acid
* gasses
* NO
* CO
* ions
* Ca2+ (not created/destroyed by enzymes, but rather reg of Ca2+ in cytoplasm/movement actively)

the effects of cAMP are mediated by what?

pKa; upon ending of cAMP, causes conformational change to release 2 catalytic subunits. these catalytic subunits target Ser/Thr to phosphorylate

how are scaffold proteins useful in 2ndary messaging?

we can restrict 2ndary messenger production to sub cellular regions to maintain specific effects