THE POSSIBLE ROLE OF HYDROGEN-SULFIDE AS AN ENDOGENOUS SMOOTH-MUSCLE RELAXANT IN SYNERGY WITH NITRIC-OXIDE

Hydrogen sulfide (H2S), which is well known as a toxic gas, is produce d endogenously in mammalian tissues from L-cysteine mainly by two pyri doxal-5'-phosphate-dependent enzymes, cystathionine beta-synthetase an d cystathionine gamma-lyase. Recently, we showed that cystathionine be ta-synthetase in the brain produces H2S, and that H2S facilitates the induction of hippocampal long-term potentiation by enhancing NMDA rece ptor activity. Here we show that mRNA for another H2S producing enzyme , cystathionine gamma-lyase, is expressed in the ileum, portal vein, a nd thoracic aorta. The ileum also expresses cystathionine beta-synthet ase mRNA. These tissues produce H2S, and this production is blocked by cystathionine beta-synthetase and cystathionine gamma-lyase specific inhibitors. Although exogenously applied H2S alone relaxed these smoot h muscles, much lower concentrations of H2S greatly enhanced the smoot h muscle relaxation induced by NO in the thoracic aorta. These observa tions suggest that the endogenous H2S may regulate smooth muscle tone in synergy with NO. (C) 1997 Academic Press.