CellSig13 - 22 Flashcards
Identify 2 types of intracellular receptors
Gases, nuclear receptors
Two gaseous ligands
NO, CO
Four nuclear receptor ligands
Steroid hormones, thyroid hormones, retinoids, vitamin D
Characterise NO
Very reactive gaseous free radical
What catalyses the production of NO?
NOS - NO synthase through two monooxygenase reactions
Outline structure of NOS
Reductase domain that binds NADPH, FMN, FAD; haem binding domain
What are the three types of NOS?
e, n and iNOS
What is important to note about eNOS and nNOS?
They are constitutively expressed - cNOS
What is different about iNOS?
Its expression is inducible
Characterise cNOS
Activity induced by Ca2/calmodulin
Characterise eNOS
Endothelial (NOS3)
Characterise nNOS
Neural (NOS1)
Characterise iNOS
Inducible (NOS2) - activity constitutively active, expression inducible
What are the main differences between cNOS and iNOS?
cNOS: calmodulin dependent, picomoles released, short-lasting release; iNOS: opposite, nanomoles released, long lasting
What is the NOS target?
Guanylyl cyclase
What was NOS originally known as and why?
EDRF - released by endothelia, relaxes smooth muscle
How does NO act in the immune system?
Kills bacteria and parasites and induces cell death
What drugs affect NO signalling?
Nitroglycerin - metabolised to NO, treats angina; viagra - inhibitor of type V phosphodiesterase, increases NO, prolonging increases in cGMP levels
Signalling molecules that bind with nuclear receptors
Cortisol, estradiol, testosterone, vitamin D3, thyroxine, retinoic acid
Outline the topography of nuclear receptors
Inhibitory proteins hold them in inactive states, ligand removes inhibitors, receptors interact with co-activators and transcription is controlled
What does RXR stand for?
Retinoid X receptor
What do all heterodimer nuclear receptors have in common?
Share a partner in RXR
What do all homodimer nuclear receptors have in common?
RE - response element
