Molecular Mechanisms of Action of Gas Transmitters NO, CO and H2S in Smooth Muscle Cells and Effect of NO-generating Compounds (Nitrates and Nitrites) on Average Life Expectancy.

Gaseous signaling molecules (gas transmitters) take an especial position among the numerous signaling molecules involved in the regulation of both intracellular processes that occur in different types of cells and cell-cell interactions. At present time, gas transmitters include three molecules whose enzymatic systems of synthesis and degradation, physiological action and intracellular effectors, the change of which under the action of gas transmitters may result in physiological and/or pathophysiological effects are well- determined. These molecules include nitrogen oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). They are involved in the regulation of functions of various organs and systems of the human body, including the circulatory system. Interaction of NO, CO and H2S with various enzymatic and structural components of endothelial and, especially, smooth muscle cells has a significant impact on vascular tone and blood pressure. Furthermore, the crossing of NO-, CO- and H2S-mediated signaling pathways at common effectors and interaction with each other can determine the end, resulting functional response of the cell. The knowledge of the molecular targets of gas transmitters' action, the structure of the binding centers for gas transmitters and their interaction with each other may be essential in the development of methods of regulation of these signaling systems by targeted, directed action. This review summarizes the molecular mechanisms of the NO, CO and H2S interaction with the main targets, which carry out their regulatory effect on vascular smooth muscle cells. Also we describe here different ways of cross-regulation of NO-, CO- and H2S-dependent signaling pathways. We analyzed NO-synthase and nitrite reductase systems of nitric oxide cycle and discuss the nitrate-nitrite background of the existence of modern man, which can substantially modify the signaling system, the metabolism of virtually all cell ultrastructure of neurons, neuron-neuron and neuron-glial interactions and exerts its influence on socially significant diseases that can affect the quality and the average life expectancy.

[Gas Signalling in Mammalian Cells].

At the end of the last century after the discovery of signaling functions of nitric oxide (NO, II), a new class of biologically active substances was admitted. It includes so-called gas transmitters acting as intercellular and intracellular regulators of different physiological functions. Currently, this class includes such gases as NO, carbon monoxide (CO) and hydrogen sulfide (H2S). It was found that these gases regulate not only functions of the. gastrointestinal tract and the cardiovascular system, where it has been determined initially, but also affect the function of the central and peripheral nervous.systems. Apparently, they constitute a single complex of gas transmitters, which easily penetrates through the membrane and regulates numerous enzymatic and non enzymatic cells reactions. This review presents the mechanisms of gas transmitters' influence on the electrical and contractile properties of smooth muscle cells (SMC) as a possible new ways to interact with the "classical" intracellular signaling cascades (Ca2+, cyclic nucleotides) and effectors systems. On account of their interactions the role of cyclic nucleotides and calcium ions in the implementation of the signal gas molecules functions is analyzed. We summarize the literature data and the results of our own research on the role of SMC membrane ion-transporting systems in myogenic effects of NO, CO and H2S and describe possible reasons of gas transmitters multidirectional influence on the excitation-contraction coupling in SMC.