autonomic NS Flashcards
What is the big picture of GPCRs?
first messenger activates GPCR with activates effector which activates second messenger which causes cellular response
What is the G protein made of?
3 subunits… alpha, beta, gama
What does a G protein do? How does it do this?
It either stimulates or inhibits an effector (enzyme or ion channel)
A Gs protein:
alpha subunit detaches from GPCR, GDP–> GTP
once first messenger disassociates, alpha subunit releases GTP and goes back to beta and gamma (now GDP again)
A Gi protein:
the alpha subunit of a Gi protein will turn off an effector
what is an effector/ its function? what are examples of them?
its function is to activate a 2nd messenger
it can either be an enzyme (like adenylate cyclase and phospholipase C) or an ion channel (we haven’t learned these)
what is the role of second messenger systems?
allows for system amplification
a single molecule initiates a process that activates a large number of physiologic changes
what are 5 second messengers we should know?
cyclic adenosine monophosphate (cAMP)
cyclic guanosine monophosphate (cGMP)
Inositol triphosphate (IP3)
Diacyglycerol (DAG)
Calcium Ion
What is the type of signal transduction of receptor a1? Its effector? its second messenger? does it increase or decrease second messenger?
Gq. increase phospholipase C. increases IP3 DAG and Ca
What is the type of signal transduction of receptor a2? Its effector? its second messenger? does it increase or decrease second messenger?
Gi. decreases adenylate cyclase. decreases camp
What is the type of signal transduction of receptor b1? Its effector? its second messenger? does it increase or decrease second messenger?
Gs. increases adenylate cyclase, increase camp.
What is the type of signal transduction of receptor b2? Its effector? its second messenger? does it increase or decrease second messenger?
Gs. increases adenylate cyclase, increase camp.
What is the type of signal transduction of receptor M1, M3, M5? Its effector? its second messenger? does it increase or decrease second messenger?
Gq. increases PLC. Increases IP3, DAG, Ca
What is the type of signal transduction of receptor M2, M4? Its effector? its second messenger? does it increase or decrease second messenger?
Gi. decreases adenylate cylcase. decreases camp
What is the Gq pathway?
- agonist binds
- alpha unit displaces GDP turns into GTP
- activates phospholipase C (cell membrane)
- PLC cleaves phosphatidylinostitol 4,5- biphosphate (PIP3) into inosital triphosphate (IP3) and diacyclgerol (DAG, which stays in membrane)
- IP3 mobilizes Ca stores in ER
- Ca activates MLC kinase, activates myosin which causes smooth muscle contratcion
- Ca also sensitizes Ca channels, allowing more in, as well as promotes activates of PKC
- DAG activates protein kinase C (PKC) –> activates phosphorylation cascade –> inhibits MLC phosphatase
What is the Gi pathway?
Inhibits adenylate cyclase to turn ATP into cAMP
What is the Gs pathway?
overall effect is increasing cAMP. but cAMP has different effects depending where it is…
cardiac (B1):
1.agonist binds.
2. activates adenylate cyclase.
3. cyclates ATP to cAMP
4. activates protein kinase A
5. PKA opens up Ca channel on cardiac myocyte as well as on SR
smooth muscle of lungs (B2)
1. same 1/2/3 steps
2. cAMP inhibits MLC kinase (no phosphorylation happening, thus no contraction)