My Dog is Broken!Suma Gondi and Kathryn Addabbo

General Information

First messenger: nitric oxide

Second messenger: cGMP

The arrows increase in size because the signal is amplified

The receptor is most likely on the cell membrane because it is an enzyme-liked receptor, meaning it has both an extracellular and intracellular domain

Cell Signaling Pathway

Cell Signaling Pathway Process

1) Nitroglycerin is converted to nitric oxide

2) Nitric oxide activates Guanylyl Cyclase, a enzyme-linked receptor

3) Guanylyl Cyclase converts GTP to cGMP

4) cGMP activates PKG

5) PKG phosphorolates proteins

6) Phospho-proteins lowers Ca2+ concentration

7) Cell membrane is desensitized to Ca2+

8) Relaxation occurs

ED Signaling Pathway

PDE5 Functioning

The normal function of PDE5 is to decrease cGMP levels by breaking it down

If PDE5 is inhibited, then cGMP levels increase, increasing the activation of PKG, decreasing calcium ion levels, and ultimately causing an increase in relaxation

If PKG is inhibited, then calcium levels will increase, causing contraction

What does Viagra do?

Inhibits PDE5 in the muscle cells

Prevents breakdown of cGMP

Allows normal cellular pathway to continue

What does Ginseng do?

An herbal plant that increases nitric oxide concentrations in cell

More activated guanylyl cylcase

greater number of cGMP

Some cGMP is broken down, but larger concentration leads to some following the normal cellular pathway

Other Possible Problems

PKG and K+ close calcium ion channelPrevents flow of calcium into cell, allowing muscle relaxation

If not blocked, there will be a flow of ions into the cell, which stops the normal cellular pathway

PKG activates MLC P’tase (removes phosphates)

Catalyzes the production of MLC, causing relaxation

If MLCK is activated, MLC will be phosphorylated, leading to contraction

Other Problems

PKG inhibits IP3 receptorsAllows calcium ions leave the ER and enter the cytosol, causing relaxation

If activated, there will be a build up of calcium ions, causing contraction

P-Lamban inhibits the calcium pumpIf activated, the levels of free Ca 2+ is reduced allowing for relaxation

If the pump is inhibited, relaxation will not occur, because high calcium levels cause contraction