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Today’s lecture

Today’s lecture. 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?

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Today’s lecture

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  1. Today’s lecture • 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.**

  2. 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

  3. 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

  4. 2nd messengers from lipids

  5. 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)

  6. 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.

  7. 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

  8. 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

  9. 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?

  10. Intestine Skeletal muscle

  11. 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

  12. Up-regulation • If the ligand concentration is low, the number of receptors can increase

  13. 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

  14. Many diseases affect signaling pathways • Cholera, cholera toxin, cells secrete ions into intestine • Myasthenia gravis, destruction of acetyl choline receptor (auto-immune)

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