Sensitizing Soluble Guanylyl Cyclase to Become a Highly CO-sensitive Enzyme

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

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Monoxide / metabolism*
  • Cattle
  • Enzyme Activation
  • Guanylate Cyclase / metabolism*
  • Recombinant Proteins / metabolism

Substances

  • Recombinant Proteins
  • Carbon Monoxide
  • Guanylate Cyclase