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. 2 nd 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 2 nd messenger NO is a soluble gas that diffuses into cells Activates soluble guanylyl cyclase  cGMP ( a 2 nd 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.  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

10. 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?

11. Intestine Skeletal muscle

12. 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 Responses decrease A receptor can be withdrawn (endocytosis) and the number of receptors declines A receptor can decrease its binding affinity for the ligand These can occur during DOWN REGULATION

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

14. 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

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