Transcript How specific is ligand

Today’s lecture
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More about G proteins
Second messengers from lipids
Calcium is a second messenger
Nitric oxide is a second messenger
more neat things about receptors and their
signaling pathways
• Do the things that you have learned about affect
homeostasis?
• **If you are on the U. Windsor Women’s Hockey
Team, please see me after class.**
How do G proteins work?
• Bind guanosine nucleotides
• When inactive bind GDP
• When activated, exchange
GTP for GDP
• Activated G proteins can open
or close a channel, or alter an
enzymes activity
2nd messengers from lipids
• Activated G protein increases the activity
of the enzyme phospholipase C (amplifier
enzyme).
• Activated phospholipase C catalyzes the
breakdown of a mb phospholipid to
diacylglyerol and inositol triphosphate
2nd messengers from lipids
Ca++ is a second messenger
• Enters the cytosol through channels
• Enters from the extracellular fluid or from
ER
• Intracellular Ca++ binds to specific proteins
 Cell activity (e.g. exocytosis, protein
movement, alter enzyme activity)
Nitric oxide is a 2nd messenger
• NO is a soluble gas that diffuses into cells
• Activates soluble guanylyl cyclase
cGMP ( a 2nd messenger)
NO from endothelial cells causes vascular smooth
muscle to relax
NO is formed from arginine by nitric oxide
synthase.
More about receptors for signaling
pathways…
• How specific is ligand-receptor binding?
• Binding site has highest affinity for 1 ligand
• E.g. a adrenergic receptor has high affinity
for norepinephrine, lower affinity for
epinephrine
More about receptors for signaling
pathways…
• Agonists and antagonists can bind onto
receptors
• Agonists stimulate the signaling pathway
• Antagonists don’t stimulate the signaling
pathway
• The basis of many pharamaceutical
products
More about receptors for signaling
pathways.
• A ligand may have different effects in different
tissues
• Epinephrine in skeletal muscle vasodilation
• Epinephrine in intestine vasoconstriction
• A ligand can bind to more than 1 receptor
protein. Why?
Intestine
Skeletal muscle
Can a cell adjust its response to a
ligand?
• Responses decrease
• A receptor can be withdrawn (endocytosis)
and the number of receptors declines
• A receptor can decrease its binding affinity
for the ligand
• These can occur during DOWN
REGULATION
Up-regulation
• If the ligand concentration is low, the
number of receptors can increase
How does the cell know when the
signal is finished?
• Muscle contraction finishes when Ca++
returns to cisternae
• Acetyl choline is broken down
• Some neurotransmitters are taken up by
cells
Many diseases affect signaling
pathways
• Cholera, cholera toxin, cells secrete ions
into intestine
• Myasthenia gravis, destruction of acetyl
choline receptor (auto-immune)