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EMBO J. 1996 Dec 16;15(24):6863-8.

Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme.

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Institut für Pharmakologie, Freie Universität Berlin, Germany.


It took at least a decade to realize that the toxic gas NO is the physiological activator of soluble guanylyl cyclase (sGC), thereby acting as a signaling molecule in the nervous and cardiovascular systems. Despite its rather poor sGC-activating property, CO has also been implicated as a physiological stimulator of sGC in neurotransmission and vasorelaxation. Here, we establish YC-1 as a novel NO-independent sGC activator that potentiates both CO- and NO-induced sGC stimulation. As this potentiating effect is also observed with protoporphyrin IX which activates sGC independently of a gaseous ligand, we conclude that stabilization of the enzyme's active configuration is the underlying mechanism of YC-1's action. Moreover, the results obtained with YC-1 reveal that CO is capable of stimulating sGC to a degree similar to NO, and thus provide the molecular basis for CO functioning as a signaling molecule.

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