The cGMP Pathway

To explain the cGMP Pathway we will take two examples.

1. The Nitric Oxide (NO)

Nitric Oxide is formed from Arginine by the enzyme Nitric Oxide synthase.

Nitric Oxide is a gas and can pass through the membrane easily.

So, NO RECEPTOR needed.

And as a result there is no G-Protein.

In a smooth muscle cell there is an enzyme that is found in the cytoplasm known as Soluble Guanylate Cyclase.

This Soluble Guanylate Cyclase is Heme containing enzyme.

The Nitric Oxide after entering the smooth muscle cell will stimulate the enzyme Guanylate Cyclase.

Guanylate Cyclase in turn will form GTP that will activate the cGMP.

The cGMP is the 2nd messenger.

The cGMP activates Protein Kinase G.

The Protein Kinase G after several steps will cause the relaxation of smooth muscles that will result in vasodilation.

It will decrease Total peripheral resistance (TPR) and hence will cause decrease in Blood pressure.

In veins it will decrease the preload resulting in decreased Cardiac output.

The receptor for ANF is a protein receptor having a single domain that goes through the cell membrane.

The ANF (also known as atrial natriuretic peptide) is the Endogenous diuretic.

There is no G Protein.

There is enzyme attached to the receptor itself.

It is the Receptor Guanylate Cyclase enzyme.

This enzyme increases the GTP that in turn will increase the cGMP (second messenger).

The cGMP will activate the Protein Kinase G which after several steps will cause the relaxation of smooth muscles of afferent arterioles.

Nesiritide is the synthetic analogue(drug) of the Atrial Natriuretic Factor that can be given in time of need.