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Sci. Signal., 28 April 2009
Vol. 2, Issue 68, p. re2
[DOI: 10.1126/scisignal.268re2]


Signaling by Gasotransmitters

Asif K. Mustafa1, Moataz M. Gadalla2, and Solomon H. Snyder1,2,3*

1 Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Gloss: Hormones, neurotransmitters, growth factors, and other signaling molecules come in different chemical classes. In recent years, a number of gases have been recognized as important messenger molecules. They include nitric oxide, carbon monoxide, and hydrogen sulfide, well known as noxious environmental pollutants, so that their existence in mammals was a surprise. All three normally regulate blood-vessel function and appear to act as neurotransmitters in addition to several other roles. Ways in which they signal to their targets, which is the subject of this Review, differ from the actions of other messenger molecules. Instead of binding to conventional receptors on the external surface of adjacent cells, the gases diffuse into the cells where nitric oxide and carbon monoxide may bind to iron in the enzyme that generates the second messenger molecular cyclic guanosine monophosphate. Nitric oxide and hydrogen sulfide can affect a wide range of proteins both on the cell surface and inside cells by chemically modifying the sulfur atom in the amino acid cysteine.

* Corresponding author. E-mail: ssnyder{at}

Citation: A. K. Mustafa, M. M. Gadalla, S. H. Snyder, Signaling by Gasotransmitters. Sci. Signal. 2, re2 (2009).

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J. B. Vicente, H. G. Colaco, M. I. S. Mendes, P. Sarti, P. Leandro, and A. Giuffre (2014)
J. Biol. Chem. 289, 8579-8587
   Abstract »    Full Text »    PDF »
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H.-F. Lu, P.-F. Wu, Y.-J. Yang, W. Xiao, J. Fan, J. Liu, Y.-L. Li, Y. Luo, Z.-L. Hu, Y. Jin, et al. (2014)
J. Neurosci. 34, 3493-3508
   Abstract »    Full Text »    PDF »
Inherent variations in CO-H2S-mediated carotid body O2 sensing mediate hypertension and pulmonary edema.
Y.-J. Peng, V. V. Makarenko, J. Nanduri, C. Vasavda, G. Raghuraman, G. Yuan, M. M. Gadalla, G. K. Kumar, S. H. Snyder, and N. R. Prabhakar (2014)
PNAS 111, 1174-1179
   Abstract »    Full Text »    PDF »
Hydrogen Sulfide Attenuates Cardiac Dysfunction After Heart Failure Via Induction of Angiogenesis.
D. J. Polhemus, K. Kondo, S. Bhushan, S. C. Bir, C. G. Kevil, T. Murohara, D. J. Lefer, and J. W. Calvert (2013)
Circ Heart Fail 6, 1077-1086
   Abstract »    Full Text »    PDF »
Molecular Biology of Atherosclerosis.
P. N. Hopkins (2013)
Physiol Rev 93, 1317-1542
   Abstract »    Full Text »    PDF »
Inhaled Carbon Monoxide Accelerates Resolution of Inflammation via Unique Proresolving Mediator-Heme Oxygenase-1 Circuits.
N. Chiang, M. Shinohara, J. Dalli, V. Mirakaj, M. Kibi, A. M. K. Choi, and C. N. Serhan (2013)
J. Immunol. 190, 6378-6388
   Abstract »    Full Text »    PDF »
The human carotid body transcriptome with focus on oxygen sensing and inflammation - a comparative analysis.
S. Mkrtchian, J. Kahlin, A. Ebberyd, C. Gonzalez, D. Sanchez, A. Balbir, E. W. Kostuk, M. Shirahata, M. J. Fagerlund, and L. I. Eriksson (2012)
J. Physiol. 590, 3807-3819
   Abstract »    Full Text »    PDF »
Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation.
C. Coletta, A. Papapetropoulos, K. Erdelyi, G. Olah, K. Modis, P. Panopoulos, A. Asimakopoulou, D. Gero, I. Sharina, E. Martin, et al. (2012)
PNAS 109, 9161-9166
   Abstract »    Full Text »    PDF »
Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway.
T. Morikawa, M. Kajimura, T. Nakamura, T. Hishiki, T. Nakanishi, Y. Yukutake, Y. Nagahata, M. Ishikawa, K. Hattori, T. Takenouchi, et al. (2012)
PNAS 109, 1293-1298
   Abstract »    Full Text »    PDF »
Hydrogen sulfide preconditioning or neutrophil depletion attenuates ischemia-reperfusion-induced mitochondrial dysfunction in rat small intestine.
Y. Liu, T. Kalogeris, M. Wang, M. Zuidema, Q. Wang, H. Dai, M. J. Davis, M. A. Hill, and R. J. Korthuis (2012)
Am J Physiol Gastrointest Liver Physiol 302, G44-G54
   Abstract »    Full Text »    PDF »
H2S: A Universal Defense Against Antibiotics in Bacteria.
K. Shatalin, E. Shatalina, A. Mironov, and E. Nudler (2011)
Science 334, 986-990
   Abstract »    Full Text »    PDF »
The Response of Caenorhabditis elegans to Hydrogen Sulfide and Hydrogen Cyanide.
M. W. Budde and M. B. Roth (2011)
Genetics 189, 521-532
   Abstract »    Full Text »    PDF »
Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis.
J. L. Sartoretto, H. Kalwa, M. D. Pluth, S. J. Lippard, and T. Michel (2011)
PNAS 108, 15792-15797
   Abstract »    Full Text »    PDF »
The therapeutic potential of hydrogen sulfide: separating hype from hope.
K. R. Olson (2011)
Am J Physiol Regulatory Integrative Comp Physiol 301, R297-R312
   Abstract »    Full Text »    PDF »
Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75.
L. Caceres, A. S. Necakov, C. Schwartz, S. Kimber, I. J. H. Roberts, and H. M. Krause (2011)
Genes & Dev. 25, 1476-1485
   Abstract »    Full Text »    PDF »
Hydrogen sulfide is a partially redox-independent activator of the human jejunum Na+ channel, Nav1.5.
P. R. Strege, C. E. Bernard, R. E. Kraichely, A. Mazzone, L. Sha, A. Beyder, S. J. Gibbons, D. R. Linden, M. L. Kendrick, M. G. Sarr, et al. (2011)
Am J Physiol Gastrointest Liver Physiol 300, G1105-G1114
   Abstract »    Full Text »    PDF »
Nitric Oxide Signaling in Brain Function, Dysfunction, and Dementia.
J. R. Steinert, T. Chernova, and I. D. Forsythe (2010)
Neuroscientist 16, 435-452
   Abstract »    PDF »
H2S Signals Through Protein S-Sulfhydration.
A. K. Mustafa, M. M. Gadalla, N. Sen, S. Kim, W. Mu, S. K. Gazi, R. K. Barrow, G. Yang, R. Wang, and S. H. Snyder (2009)
Science Signaling 2, ra72
   Abstract »    Full Text »    PDF »
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J. Neurosci. 29, 12717-12721
   Abstract »    Full Text »    PDF »

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