Nobel Prize - L-arginine / Ferid Murad, Robert Furchgott, & Louis Ignarro
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NOBELFÖRSAMLINGEN KAROLINSKA INSTITUTET THE NOBEL ASSEMBLY AT THE KAROLINSKA INSTITUTE
12 October 1998
The Nobel Assembly at the Karolinska Institute has today decided to award the Nobel Prize in Physiology jointly to Robert F. Furchgott, Louis J. Ignarro and Ferid Murad for their discoveries concerning "nitric oxide as a signaling molecule."
| Ferid Murad, MD and pharmacologist, now in Houston, Texas, analyzed how nitroglycerin and related vasodilating compounds act and discovered in 1977 that they release nitric oxide. He was fascinated by the concept that a gas could regulate important cellular functions and speculated that endogenous factors might also act through NO. However, there was no experimental evidence to support this idea at the time. |  |
| Robert F. Furchgott is a pharmacologist in New York. In 1980, he demonstrated in an ingenious experiment showing that acetylcholine dilates blood vessels only if the endothelium was intact. He concluded that blood vessels are dilated because the endothelial cells produce an unknown signal molecule that makes vascular smooth muscle cells relax. He called this signal molecule EDRF, the endothelium-derived relaxing factor, and his findings led to a quest to identify the factor. |  |
| Louis
J. Ignarro, pharmacologist in Los Angeles, participated in the
quest for EDRF´s chemical nature. He performed a brilliant series
of analyses and concluded in 1986, together with and independently of
Robert Furchgott, that EDRF was identical to NO. The problem was
solved and Furchgott's endothelial factor identified.
When Furchgott and Ignarro presented their conclusions at a conference in July, 1986, it elicited an avalanche of research activities in many different laboratories around the world. This was the first discovery that a gas can act as a signal molecule in the organism. |
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Summary
Nitric oxide (NO) is a gas that
transmits signals in the organism. Signal transmission by a gas that is
produced by one cell, penetrates through membranes and regulates the function
of another cell represents an entirely new principle for signaling in
biological systems. The discoverers of NO as a signal molecule are awarded
the 1998 Nobel Prize.
Background
It was a sensation that this
simple, common air pollutant, which is formed when nitrogen burns, for
instance in automobile exhaust fumes, could exert important functions in the
organism. It was particularly surprising since NO is totally different from
any other known signal molecule and so unstable that it is converted to
nitrate and nitrite within 10 seconds. NO was known to be produced in bacteria
but this simple molecule was not expected to be important in higher animals
such as mammals.
Further research results rapidly confirmed that NO is a signal molecule of key importance and it was also found to exert a series of other functions. We know today that NO acts as a signal molecule in the nervous system and as a gate keeper of blood flow to different organs. NO is present in most living creatures and made by many different types of cells. When NO is produced by the innermost cell layer of the arteries, the endothelium, it rapidly spreads through the cell membranes to the underlying muscle cells. Their contraction is turned off by NO. When NO is formed in nerve cells, it spreads rapidly in all directions, activating all cells in the vicinity. This can modulate many functions. When NO is produced in white blood cells (such as macrophages), huge quantities are achieved.
Nitroglycerin
Alfred Nobel invented dynamite, a
product in which the explosion-prone nitroglycerin is curbed by being absorbed
in kieselguhr, a porous soil rich in shells of diatoms. When Nobel was
taken ill with heart disease, his doctor prescribed nitroglycerin. Nobel
refused to take it, knowing that it caused headache and ruling out that it
could eliminate chest pain. In a letter, Nobel wrote: It is ironical that I
am now ordered by my physician to eat nitroglycerin. It has been known since
last century that the explosive, nitroglycerin, has beneficial effects against
chest pain.
However, it would take 100 years until it was clarified that nitroglycerin acts by releasing NO gas.
It is well-known in the scientific community that L-arginine is required for the body to synthesize nitric oxide (NO), which enables the arterial system to retain its youthful elasticity. Nitric oxide also helps to produce endothelial relaxation factor, which is needed by the arterial system to expand and contract with each heartbeat.
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