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Hydrogen sulfide: a gasotransmitter of clinical relevance

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Abstract

Though the existence of hydrogen sulfide (H2S) in biological tissues has been known for over 300 years, it is the most recently appreciated of the gasotransmitters as a physiologic messenger molecule. The enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) had long been speculated to generate H2S, and inhibitors of these enzymes had been employed to characterize influences of H2S in various organs. Definitive evidence that H2S is a physiologic regulator came with the development of mice with targeted deletion of CSE and CBS. Best characterized is the role of H2S, formed by CSE, as an endothelial derived relaxing factor that normally regulates blood pressure by acting through ATP-sensitive potassium channels. H2S participates in various phases of the inflammatory process, predominantly exerting anti-inflammatory actions. Currently, the most advanced efforts to develop therapeutic agents involve the combination of H2S donors with non-steroidal anti-inflammatory drugs (NSAIDs). The H2S releasing moiety provides cytoprotection to gastric mucosa normally adversely affected by NSAIDs while the combination of H2S and inhibition of prostaglandin synthesis may afford synergistic anti-inflammatory influences.

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Acknowledgments

This work has been supported by National Institutes of Health Medical Scientist Training Program Award (T32 GM007309) to M.S.V. and US Public Health Service Grants (MH018501) to S.H.S.

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  1. The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    M. Scott Vandiver & Solomon H. Snyder

  2. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    M. Scott Vandiver & Solomon H. Snyder

  3. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Solomon H. Snyder

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Vandiver, M.S., Snyder, S.H. Hydrogen sulfide: a gasotransmitter of clinical relevance. J Mol Med 90, 255–263 (2012). https://doi.org/10.1007/s00109-012-0873-4

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