Hydrogen Sulfide Stimulates Cyclic AMP Formation In Mammalian Retina Through the Adenylyl Cyclase Pathway

Abstract

We tested the hypothesis that Hydrogen sulfide (H2S) stimulates the formation of cyclic AMP (cAMP) in neural retina of pigs and cows via activation of the adenylyl cyclase pathway.MethodsIsolated bovine and porcine retina were exposed to H2S donors, NaHS, Na2S, the cyclic nucleotide phosphodiesterase (PDE) inhibitor, IBMX and/or the diterpene activator of adenylate cyclase, forskolin and prepared for cAMP content by EIA.ResultsThe PDE inhibitor, IBMX (2 mM) caused a two‐three fold increase in basal cAMP levels in bovine and porcine retina respectively. The combination of both IBMX and forskolin (10 μM) produced a synergistic increase (p < 0.001) in cAMP levels over basal. NaHS (10 nM‐1 μM), and Na2S (10 nM‐100 μM) increased cAMP in both tissues. For instance, 100 nM NaHS caused an increase of 20% in bovine retina whilst 1 μM NaHS produced a 15% increase in porcine retina. In bovine and porcine retina, the effects caused by forskolin on cAMP production were not potentiated by addition of low or high concentrations of NaHS or Na2S.ConclusionsBoth NaHS and Na2S significantly increased cAMP levels in bovine and porcine retinae indicating that this nucleotide serves as a mediator of effects caused by H2S. Furthermore, effects produced by forskolin on cAMP formation were not additive with those elicited by H2S donors postulating that these agents may share a common mechanism in their action on the adenylyl cyclase pathway.