Guanylate Cyclase Signaling

Question 1

What can happen due to prolonged bed rest?

Answer 1

An increased blood volume due to ‘atrial stretch’; A sustained increase in cardiac filling pressure. Causes release of atriopeptigen by atrial cardiocytes.

Question 2

What is atriopeptigen?

Answer 2

A prohormone that is then activated into atriopeptin.

Question 3

What does atriopeptin do in the adrenal gland?

Answer 3

Decreases aldosterone secretion; Increases sodium excretion.

Question 4

What does atriopeptin do in the kidney?

Answer 4

Decreases renin and angiotensin secretion; Increases sodium excretion and decreases blood volume

Question 5

What does atriopeptin do in the blood vessels?

Answer 5

Relaxes vascular smooth muscle; Decreases blood pressure due to vasodilation

Question 6

Discuss the signal transduction mechanism in smooth muscle.

Answer 6

1. Atriopeptin binds its receptor on smooth muscle.
2. Guanylate cyclase is activated and turns GTP into cGMP
3. This activates Protein Kinase G; Activates Myosin L-chain kinase
4. Causes smooth muscle relaxation.

Question 7

Which two enzymes regulate the contraction of smooth muscle?

Answer 7

1. Myosin L-chain phosphatase (stimulated by cGMP) removes the phosphate from myosin, causing a low affinity for actin; No contraction.
2. Myosin L-chain Kinase which does the opposite.

Question 8

Discuss the regulation of Myosin L-chain kinase.

Answer 8

Positive: Binding to calcium calmodulin complex.
Negative: Phosphorylation by PKA or PKG which lowers its ability to bind calcium-calmodulin.

Question 9

What is the role of Nitric oxide synthase?

Answer 9

It takes the guanidino group of arginine and oxygen and makes nitric oxide and citruline; It is a soluble receptor

Question 10

Describe the NO signaling pathway in the endothelial cell

Answer 10

1. ACh binds to a receptor; Activates Gq
2. Gq activates PLC beta; Cleaves PIP2
3. IP3 goes to its receptor on SR.
4. Increased calcium activates NO synthase.

Question 11

Describe the NO signaling pathway in the smooth muscle cell

Answer 11

1. NO activates guanylyl cyclase.
2. Guanylyl cyclase makes cGMP from GTP; Activating PKG
3. PKG activates phosphorylates target protein (MLCK)
4. Inhibits MLCK activity; Smooth muscle relaxation.

Question 12

What else can nitric oxide do?

Answer 12

Can inhibit platelet aggregation; Dilates blood vessels.