Signalling via intracellular receptors Flashcards
Which signals can pass through the membrane to interact with intracellular receptors?
- Small molecules
- Hydrophobic molecules
What do cell-surface receptors do?
Bind hydrophillic signals (can’t cross the membrane) and TRANSDUCE the signals into an intracellular response
How do molecules that bind intracellular receptors get into the cell?
Diffuse straight through the membrane
OR
Use carrier proteins
Which 4 molecules bind to nuclear receptors?
1) Steroid hormones (testosterone, cortisol, estradiol)
2) Thyroid hormones (thyroxine)
3) Retinoids (retanoic acid - Vitamin A)
4) Vitamin D
What gases bing to intracellular receptors?
Nitric oxide (NO) Carbon monoxide (CO)
What are 3 properties of NO?
1) Very small (only 2 atoms)
2) Gaseous
3) Free radical
What is a free radical and what can it do?
Unpaired electron in the outer shell
Very reactive
Can damage other proteins
What are other nitric gases that are quite stable?
Nitrogen Dioxide (NO2) Nitrous Oxide (N2O)
How is NO made?
- Substrate of L-arginine (an amino acid)
- 2 successive oxidations
- Producing L-citrulline, NO and water
What enzyme produces NO from L-arginine?
NOS (Nitric oxide synthase)
What is important about NOS?
Comes in various varieties, which are specific for function
What is cNOS?
Constitutive NOS - when transcribed in the cell they are expressed all of the time
How is the enzymatic activity of cNOS induced?
How long does the activity last for?
By Ca2+/Calmodulin
Activity is short-lived
How much NO does cNOS produce?
Very small amounts (picomoles)
What are the 2 representatives of cNOS?
eNOS (endothelial)
nNOS (neural)
Where is eNOS present?
At the CELL MEMBRANE
Expressed in:
- Endothelium
- Cardiac myocytes
- Osteoblasts/osteoclasts
- Platelets
What is nNOS present?
In the CYTOSOL
Expressed in:
- CNA
- NANC neurons
- ENS
- Retina
What is eNOs important in?
Vasculature
What is iNOS?
Inducible NOS
How is iNOS different to cNOS?
Expression is inducible but the enzymatic activity is constitutive
Where as cNOS - the expression is constitutive but the enzymatic activity is regulated
iNOS also has a long-lasting effect and produces more NO
When is iNOS transcriptionally induced?
In response to pathological stimuli (LPS, IFN-g, IL-1)
Where is iNOS expressed?
- Macrophages and Kupffer cells
- Neutrophills
- Fibroblasts
- Vascular smooth muscle and endothelial cells