autonomic NS

Question 1

What is the big picture of GPCRs?

Answer 1

first messenger activates GPCR with activates effector which activates second messenger which causes cellular response

Question 2

What is the G protein made of?

Answer 2

3 subunits… alpha, beta, gama

Question 3

What does a G protein do? How does it do this?

Answer 3

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

Question 4

what is an effector/ its function? what are examples of them?

Answer 4

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)

Question 5

what is the role of second messenger systems?

Answer 5

allows for system amplification
a single molecule initiates a process that activates a large number of physiologic changes

Question 6

what are 5 second messengers we should know?

Answer 6

cyclic adenosine monophosphate (cAMP)
cyclic guanosine monophosphate (cGMP)
Inositol triphosphate (IP3)
Diacyglycerol (DAG)
Calcium Ion

Question 7

What is the type of signal transduction of receptor a1? Its effector? its second messenger? does it increase or decrease second messenger?

Answer 7

Gq. increase phospholipase C. increases IP3 DAG and Ca

Question 8

What is the type of signal transduction of receptor a2? Its effector? its second messenger? does it increase or decrease second messenger?

Answer 8

Gi. decreases adenylate cyclase. decreases camp

Question 9

What is the type of signal transduction of receptor b1? Its effector? its second messenger? does it increase or decrease second messenger?

Answer 9

Gs. increases adenylate cyclase, increase camp.

Question 10

What is the type of signal transduction of receptor b2? Its effector? its second messenger? does it increase or decrease second messenger?

Answer 10

Gs. increases adenylate cyclase, increase camp.

Question 11

What is the type of signal transduction of receptor M1, M3, M5? Its effector? its second messenger? does it increase or decrease second messenger?

Answer 11

Gq. increases PLC. Increases IP3, DAG, Ca

Question 12

What is the type of signal transduction of receptor M2, M4? Its effector? its second messenger? does it increase or decrease second messenger?

Answer 12

Gi. decreases adenylate cylcase. decreases camp

Question 13

What is the Gq pathway?

Answer 13

1. agonist binds
2. alpha unit displaces GDP turns into GTP
3. activates phospholipase C (cell membrane)
4. PLC cleaves phosphatidylinostitol 4,5- biphosphate (PIP3) into inosital triphosphate (IP3) and diacyclgerol (DAG, which stays in membrane)
5. IP3 mobilizes Ca stores in ER
6. Ca activates MLC kinase, activates myosin which causes smooth muscle contratcion
7. Ca also sensitizes Ca channels, allowing more in, as well as promotes activates of PKC
8. DAG activates protein kinase C (PKC) –> activates phosphorylation cascade –> inhibits MLC phosphatase

Question 14

What is the Gi pathway?

Answer 14

Inhibits adenylate cyclase to turn ATP into cAMP

Question 15

What is the Gs pathway?

Answer 15

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)

Question 16

What is the physiologic response of the B1 receptor in myocardium and conduction system?

Answer 16

Increased contractility, increased HR, increased conduction speed

Question 17

What is the physiologic response of the M2 receptor in myocardium and conduction system?

Answer 17

decreased contractility, decreased HR, decreased CV

Question 18

Which receptors are in the arterial smooth muscle VASCULATURE? What is the physiologic response?

Answer 18

a1> a2. vasoconstriction

a1= Gq
a2= Gi

Question 19

Which receptors are in the venous smooth muscle VASCULATURE? What is the physiologic response?

Answer 19

a2 > a1. vasoconstriction

a2= Gi
a1=Gq

Question 20

Which receptors are in the myocardium smooth muscle VASCULATURE? What is the physiologic response?

Answer 20

B2. vasodilation

b2= Gs

Question 21

What receptors are in the skeletal muscle smooth muscle VASCULATURE? what is the physiologic response?

Answer 21

B2.Vasodilation

B2= Gs

Question 22

What receptors are in the renal bed smooth muscle VASCULATURE? what is the physiologic response?

Answer 22

DA. vasodilation

Gi

Question 23

What receptors are in the mesenteric muscle smooth muscle VASCULATURE? what is the physiologic response?

Answer 23

DA. vasodilaton

Gi

Question 24

What receptors are in the bronchial tree? what is the physiologic response?

Answer 24

B2. bronchodilation
M3. Bronchoconstriction

Question 25

what receptors are in renal tubules? what is the physiologic response?

Answer 25

a2. diuresis (ADH inhibition)

Question 26

what does B1 stimulation in kidneys cause?

Answer 26

increased renin release

Question 27

where is the location of a2 receptors ? role in each place?

Answer 27

presynaptic - Gi. decreases release of NE
postsynaptic- smooth muscle and several organs. Gi

Question 28

why does dexmetodomine transiently increase BP?

Answer 28

rapid admin causes a2 receptors on postsynaptic smooth muscle vasculature in arterial and venous circulation to constrict. CNS effect lags behind (ultimately this will kick in to increase SNS tone, and bring down BP)