Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Author/Curator: Aviral Vatsa PhD, MBBS

Nitric oxide (NO) is of extreme biological interest due to its wide range of physiological functions in almost all the human systems. For long it has been of vital interest to chemists, environmental scientists, metallurgists and other domains. It is only recently that the world of biology has discovered the ubiquitous presence of this small molecule in human body and the scientific exploration of its effects has grown ever since. It was only in 1980s that three different groups demonstrated that NO is indeed produced by mammalian cells and that NO has specific biological roles in the human body. These studies highlighted the role of NO in cardiovascular, nervous and immune systems. In cardiovascular system NO was shown to cause relaxation of vascular smooth muscle cells causing vasodilatation, in nervous system NO acts as a signalling molecule and in immune system it is used against pathogens by the phagocytosis cells. These pioneering studies opened the path of investigation of role of NO in biology. In 1998, three scientists, Robert F Furchgott, Louis J Ignarro, and Ferid Murad, were awarded Nobel Prize for their discoveries concerning ‘nitric oxide as a signalling molecule’.

Since then hundreds and thousands of publications have appeared in the scientific literature. These studies have attributed a wide range of biological functions to NO. A few important examples are:

• toxic free radical causing injury to proteins, lipids and DNA
• mediator of synaptic plasticity
• intercellular neuronal signalling molecule
• pro and anti inflammatory molecule
• role in cell degeneration and ischaemia-reperfusion injury
• role in atherosclerosis and inherited motor disorders
• role in bone remodelling

The above list is by no means exhaustive, but it gives an idea about the ubiquitous involvement of NO in human systems.

Since NO has been implicated in various disease states, it has also been a prime target to achieve therapeutic benefits. Efforts are ongoing to investigate the therapeutic potential of NO in cardiovascular diseases, sepsis and shock, respiratory ailments, neuronal disease and bone conditions…just to name a few.

Although a lot of progress has happened in our understanding of this small molecule since its discovery, but still there are many challenges that the researchers face today while investigating NO. These are primarily because NO is metabolised very quickly (<5 sec) and it can difuse freely across cellular membranes owing to its chemical structure. This is the precise reason why it can act as a potent signaling molecule across systems in the first place. New techniques are appearing to delineate the role of NO at sub-cellular level and have promising potential to aid NO research in the future.

In the future posts on this topic I will strive to cover different aspects of NO physiology and its role in various disease conditions, techniques for NO detection, signaling mechanism etc.

Sources:

1. The nature of endothelium-derived vascular relaxant factor

Nature 308, 645 – 647 (12 April 1984); doi:10.1038/308645a0

T. M. Griffith, D. H. Edwards, M. J. Lewis, A. C. Newby & A. H. Henderson

2. Nitric oxide: physiology, pathophysiology, and pharmacology.

Pharmacological Rev June 1991 43:109-142

S Moncada, R M Palmer, and E A Higgs

3. Introduction to EDRF research.

J Cardiovasc Pharmacol.1993;22 Suppl 7:S1-2.

Furchgott RF

4. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1998/illpres/