Nitric oxide

Nitric oxide (NO) is a highly diffusible, short-lived, endogenously formed bioactive molecule. It is found in neurons as well as in endothelial and immune cells. Nitric oxide is formed by catalysis of the enzyme nitrogen monoxide synthase (NOS). NOS (NO synthase) catalyses the reaction of L-arginine to nitrogen monoxide and LCitrulline.

Nitric oxide, or NO, is a central regulator of the vascular system, an unconventional transmitter or neuromodulator (nitrergic neurons) that leads to vascular relaxation after stimulation with acetylcholine.

NO is released from L-arginine by NO synthetases (NOS), of which three isoforms have been described so far:

• the neuronal NOS (nNOS). The expression takes place constitutively in nitrergic nerve cells
• the endothelial NOS (eNOS). The expression of eNOS occurs in vascular endothelial cells
• the inducible NOS (iNOS). Its expression is induced in inflammatory cells during inflammatory processes.

The point of attack of NO lies in the intracellular space of the successful cells. NO plays a role in the CNS as well as in the periphery. NO directly prevents the adhesion and aggregation of thrombocytes.

Several special features distinguish NO from other neurotransmitters. In contrast to other transmitters, NO is an inorganic molecule, which is also gaseous and thus completely permeable to the membrane. NO is not stored in vesicles.

Neuronally produced NO is extremely short-lived. The inorganic molecule easily diffuses through biological membranes and can cover distances of up to 200 µm in the neuronal system.

The receptor for NO is not a cell membrane protein, but a soluble guanylate cyclase (GCS). This is a cytoplasmic enzyme that catalyses the synthesis of GTP to cGMP, which in turn acts as an intracellular 2nd messenger. cGMP activates the cGMP-dependent protein kinase G (PKG), which is responsible for the synthesis of various proteins. PKG phosphorylates various protein substrates, thereby causing smooth muscle relaxation.

In the central nervous system NO is involved in the long-term modulation of synaptic transmissions, in the peripheral nervous system it serves as an atypical neurotransmitter (atypical because the target molecule is not a membrane receptor but an intracellular enzyme).

NO normally occurs in the form of a radical, and as such is highly cytotoxic and bacteriostatic. This explains the need for rapid elimination of NO. In biological fluids, nitric oxide is oxidized to nitrite and nitrate within a few seconds. Since these inorganic molecules are about 1000 times less effective than NO, it can be assumed that the oxidation serves to inactivate the NO.

What is certain is that NO from nitrergic neurons is responsible for vasodilation in the erectile tissue of the penis and thus for erection. Furthermore, nitrergic neurons in the autonomous intestinal system are responsible for the relaxing component of the peristaltic wave.

S.a. among nitrovasodilators

1. Graefe KH et al. Anatomical and physiological principles . In: Graefe KH et al (Eds) Pharmacology and Toxicology . Georg Thieme Publisher Stuttgart S.163-164
2. Neumann HA (2014) The coagulation system. ABW-Scientific Publisher GmbH Berlin