, 2008 and Morikawa et al., 2012). Spatial relations among the gas-producing enzymes and their receptor systems are

certainly an important factor to take into account. Another Selumetinib nmr important factor is the tissue concentrations of relevant gases. Morikawa et al. further demonstrated the potential for interactions of O2, CO, H2S by measuring endogenous CO and H2S concentrations of the brain exposed varied O2 concentrations. While hypoxia causes a decrease in CO concentrations and an increase in H2S, HO-2-null mice do not exhibit such an O2-dependent alteration of CO and H2S. Olson et al. (2006) postulated an interesting hypothesis that H2S catabolism serves as an intrinsic O2 sensor based on their results that H2S is inversely related with O2 in the trout gill chemoreceptors and pulmonary arteries of some mammalian species (Olson and Whitfield, 2010). Olson suggests that the relation of H2S and O2 can be analogous to the yin and yang and that the amount of H2S itself is a universal O2 sensor. Not only the production but also degradation of H2S determines

the effective Dinaciclib concentration of this gas. Regarding H2S catabolism, sulfide-quinone reductases (SQR), the disulfide oxidoreductase flavoprotein superfamily, has gained much attention as it contributes to H2S oxidation by phototrophic bacteria wherein H2S donates electrons to the respiratory chain (Griesbeck et al., 2000). Whether or not SQR exists and/or plays roles in H2S metabolism in the mammalian CNS is currently controversial (Ackermann et al., 2011, Lagoutte et al., 2010 and Linden et al., 2011). The oxidation of H2S on the mitochondrial respiratory chain

adds complexity in the O2–H2S signaling (Bouillaud and Blachier, 2011) and deserves further investigation. What might be the feasible approaches to investigate such complexity and Adenosine triphosphate polymodal nature of gas interactions? Here we consider some of the governing factors controlling local gas amounts and actions; these include: (i) substrate and/or cofactor availability; (ii) enzyme control resulting from allosteric control and covalent modification; (iii) spatial distribution of enzyme expression in the tissue; and (iv) temporal regulation of gas generation. One approach is imaging mass spectrometry combined with quantitative metabolomics which satisfy several criteria as it can provide quantitative dynamics of many metabolites simultaneously with spatio-temporal resolution. Hattori et al. (2010) combined two types of mass spectrometry (MS); matrix-assisted laser desorption ionization (MALDI)/MS and capillary-electrophoresis/electrospray ionization (CE/ESI)/MS. Unlike conventional spectroscopic techniques with which chemical profiles are obtained from one selected volume at a time, MALDI/MS has strengths in visualizing multiple metabolites in discrete areas with a single laser ablation (Harada et al., 2009, Kubo et al., 2011 and Stoeckli et al., 2001) (Fig. 4A). However, it still requires further efforts to be supported for quantification.