Nitric oxide in neurotransmission

Abstract

Nitric Oxide and Free Radicals in Peripheral Neurotransmission [Series: Nitric Oxide in Biology and Medicine (J. R. Lancaster and T.D. Giles, eds)]edited by Stanley Kalsner, Birkhauser, 2000. DM188 (hardback)ISBN 0 8176 4070 3Nitric Oxide and Free Radicals in Peripherial Neurotransmission is the second volume in the series Nitric Oxide in Biology and Medicine, a series that will contain books that summarize current knowledge of the role of nitric oxide (NO) in biology and medicine.Autonomic nerves were originally characterized as either cholinergic or adrenergic based on whether they used acetylcholine or noradrenaline, respectively, as transmitters. The discovery that noradrenergic, noncholinergic (NANC) nerves innervate smooth muscle in the lower regions of the gut opened an avenue for realizing that other inhibitory transmitters, including NO, exist. The main steps in the discovery of NO as an extracellular messenger were taken when the endothelium-derived relaxing factor (EDRF) was identified as NO. When Furchgott and Ignarro published their conclusions in 1986, an avalanche of research activities followed in many different laboratories around the world. This was the first discovery that a gas can act as a signal molecule in living organisms, and the discoverers, Robert F. Furchgott, Louis J. Ignarro and Ferid Murad, were awarded the Nobel Prize in 1998.The NO story started in 1980 when Furchgott, a pharmacologist in New York, demonstrated in an ingenious experiment that acetylcholine dilated blood vessels only if the endothelium of blood vessels was intact. He concluded that the 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.In terms of the criteria for defining whether an endogenous ligand is a transmitter, it seems that NO differs significantly from the classical transmitters. This unique substance is not stored in vesicles or released by a conventional stimulus–secretion coupling mechanism, and it does not act at cell-membrane-associated receptors. Instead, NO binds to the heme moiety of guanylyl cyclase, resulting in a conformational change and activation of the enzyme and production of cGMP. In this respect, the heme group of guanylyl cyclase can be considered the receptor for NO. NO is a common air pollutant, which is formed when nitrogen burns, for example, in automobile exhaust fumes. Thus, NO is totally different from any other known signal molecule and so unstable that it is converted to nitrate and nitrite within ten seconds. If it is synthesized once on demand, it diffuses far away. How and why it is synthesized is yet to be classified.NO is one of the smallest and most diffusible molecules released without being stored and is able to spread rapidly through the cell membrane and to diffuse far away from where it was synthesized. It fulfills the expectation from non-synaptically active transmitters. In fact, the discovery of NO provided strong support for the non-synaptic communication concept existing in the brain and periphery. According to this concept a neuron is able to interact with another neuron without synaptic contact: the transmitter released from the axon terminal into the extracellular space diffuses a few hundred micrometers and activates high-affinity receptors. Recent development in the NO story is that NO plays a role in penile erectile tissues. NO can initiate erection of the penis by dilating the blood vessels to the erectile bodies. This progress has already led to the development of new drugs against impotence.This book is an excellent example of how it is possible to provide reviews that are interesting not only for those who want to become familiar with NO but also for those who have been working in this research area for years – not an easy task in a field that develops exponentially! Despite these difficulties, the book succeeded by inclusion of authors whose contribution to this research area has been significant; indeed, many of these authors are still active in this field. This impressive list of contributors is one of the main assets of the book, although a few more illustrations and diagrams would have been helpful, particularly in the otherwise very clear chapter by Karl Erik Andersson on ‘Nitrergic Neurotransmission on the Lower Urinary Tract and Penile Erectile Tissues’. The main thrust of the book is the multiplicity of molecular, pharmacological and clinical approaches for understanding a wide range of physiological and pathophysiological effects of NO. As such, this book covers all the important topics with chapters on biochemistry, pathophysiology and clinical aspects in atheroclerosis, bacterial infections (sepsis and circulatory shock), cancer treatment, inflammatory diseases and impotence. The greatest strength of the book is that it speaks the language of the neurobiologist and clinician, and therefore it will be a useful guide not only for newcomers to the field, but also for active scientists and clinicians.