Physiological and pharmacological features of the novel gasotransmitter: hydrogen sulfide.
Hydrogen sulfide (H(2)S) has been known for hundreds of years because of its poisoning effect. Once the basal bio-production became evident its pathophysiological role started to be investigated in depth. H(2)S is a gas that can be formed by the action of two enzymes, cystathionine gamma-lyase and cystathionine beta-synthase, both involved in the metabolism of cysteine. It has several features in common with the other two well known "gasotransmitters" (nitric oxide and carbon monoxide) in the biological systems. These three gasses share some biological targets; however, they also have dissimilarities. For instance, the three gases target heme-proteins and open K(ATP) channels; H(2)S as NO is an antioxidant, but in contrast to the latter molecule, H(2)S does not directly form radicals. In the last years H(2)S has been implicated in several physiological and pathophysiological processes such as long term synaptic potentiation, vasorelaxation, pro- and anti-inflammatory conditions, cardiac inotropism regulation, cardioprotection, and several other physiological mechanisms. We will focus on the biological role of H(2)S as a molecule able to trigger cell signaling. Our attention will be particularly devoted on the effects in cardiovascular system and in cardioprotection. We will also provide available information on H(2)S-donating drugs which have so far been tested in order to conjugate the beneficial effect of H(2)S with other pharmaceutical properties.
Mancardi
Daniele
D
Department of Clinical and Biological Sciences, University of Turin, Italy. daniele.mancardi@unito.it
Penna
Claudia
C
Merlino
Annalisa
A
Del Soldato
Piero
P
Wink
David A
DA
Pagliaro
Pasquale
P
D000818:Animals; D002319:Cardiovascular System / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D005740:Gases / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology
D005740:Gases; D013440:Sulfides; D009569:Nitric Oxide; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide