The role of hydrogen sulfide in cyclic nucleotide signaling.

Hydrogen sulfide (HS) is recognized as an endogenous gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). By integrating into multiple signaling pathways, HS elicits biological functions in various mammalian systems. Among these pathways, cyclic nucleotide signaling has gradually gained attention in the past decade. Based on current evidence, it seems that HS may differentially affect the activity of resting adenylyl cyclases (ACs) and activated ACs, therefore playing a dual role in the regulation of cyclic adenosine monophosphate (cAMP) mediated signaling. However, how HS achieves the differential regulation on ACs remains unknown at molecular level. In the context of cyclic guanosine monophosphate (cGMP) regulation, HS augments its downstream signaling at least through three different mechanisms: (1) HS potentiates the response of soluble guanylyl cyclases (sGCs) to NO; (2) HS inhibits activity of phosphodiesterases (PDEs); and (3) HS enhances the production of NO. By regulating cyclic nucleotide signaling, HS possesses therapeutic potentials particularly for hypertension and cardiac injury which have also been discussed in the current review. Nevertheless, a detailed portrayal of HS mediated interaction with target proteins is still required for a better understanding of the role of this important gaseous mediator in regulating cyclic nucleotide signaling.