Role of protons in calcium signaling.

Thirty-six years after the publication of the important article by Busa and Nuccitelli on the variability of intracellular pH (pHi) and the interdependence of pHi and intracellular Ca2+ concentration ([Ca2+]i), little research has been carried out on pHi and calcium signaling. Moreover, the results appear to be contradictory. Some authors claim that the increase in [Ca2+]i is due to a reduction in pHi, others that it is caused by an increase in pHi. The reasons for these conflicting results have not yet been discussed and clarified in an exhaustive manner. The idea that variations in pHi are insignificant, because cellular buffers quickly stabilize the pHi, may be a limiting and fundamentally wrong concept. In fact, it has been shown that protons can move and react in the cell before they are neutralized. Variations in pHi have a remarkable impact on [Ca2+]i and hence on some of the basic biochemical mechanisms of calcium signaling. This paper focuses on the possible triggering role of protons during their short cellular cycle and it suggests a new hypothesis for an IP3 proton dependent mechanism of action.

Environmental and Endogenous Acids Can Trigger Allergic-Type Airway Reactions.

Inflammatory allergic and nonallergic respiratory disorders are spreading worldwide and often coexist. The root cause is not clear. This review demonstrates that, from a biochemical point of view, it is ascribable to protons (H+) released into cells by exogenous and endogenous acids. The hypothesis of acids as the common cause stems from two considerations: (a) it has long been known that exogenous acids present in air pollutants can induce the irritation of epithelial surfaces, particularly the airways, inflammation, and bronchospasm; (b) according to recent articles, endogenous acids, generated in cells by phospholipases, play a key role in the biochemical mechanisms of initiation and progression of allergic-type reactions. Therefore, the intracellular acidification and consequent Ca2+ increase, induced by protons generated by either acid pollutants or endogenous phospholipases, may constitute the basic mechanism of the multimorbidity of these disorders, and environmental acidity may contribute to their spread.

Is hydrogen ion (H(+)) the real second messenger in calcium signalling?

Most second messengers have the acknowledged ability to mobilize the segregated Ca(2+) from intracellular stores, although the mechanisms of mobilization are unclear. To study this problem, the fact that inositol 1,4,5-trisphosphate, and six other known endogenous Ca(2+) mobilizers are acids, or acid-generating compounds, is highlighted. In physiological conditions, a newly generated acid releases H(+). The transient rise of H(+) in the cytosol may induce the lowering of pH, mobilization of bound Ca(2+), protein conformational rearrangement, store depletion, and Ca(2+) influx. Accordingly, a new description of the basic mechanism for signal transduction in non-excitable cells and the related consequences is put forward.

Respiratory allergies: a general overview of remedies, delivery systems, and the need to progress.

The spread of respiratory allergies is increasing in parallel with the alarm of the scientific community. Evidently, our knowledge of the onset mechanisms of these diseases and, as a consequence, of the available remedies is inadequate. This review provides a brief, general description of current therapeutic resources and the state of research with regard to both drugs and medical devices in order to highlight their limits and the urgent need for progress. Increasing the amount of basic biochemical research will improve our knowledge of such onset mechanisms and the potential efficacy of therapeutic preparations.