cyclic GMP

Cyclic GMP is cyclic AMP's quieter sibling — a second messenger built on the same plan but running its own pathway. Its signature job is relaxation: in blood vessels, a rise in cyclic GMP makes smooth muscle let go, widening the vessel.

It is made by guanylyl cyclase from GTP. There are two forms of the enzyme: a soluble cytoplasmic form switched on by nitric oxide, and a membrane-bound form switched on by peptides such as atrial natriuretic peptide. Cyclic GMP works mainly by activating protein kinase G, which relaxes smooth muscle, and (in the eye) by directly gating ion channels in the retina's light-sensing cells. Like cyclic AMP, it is broken down by phosphodiesterases.

This pathway is the basis of several important drugs. Organic nitrates such as glyceryl trinitrate release nitric oxide to raise cyclic GMP and relieve angina. Sildenafil and related drugs inhibit phosphodiesterase type 5, which normally degrades cyclic GMP, so cyclic GMP persists — relaxing vascular smooth muscle in the penis (erectile dysfunction) or pulmonary arteries (pulmonary hypertension). The same logic explains why combining nitrates with PDE5 inhibitors can cause dangerous hypotension.