Organ design for generation and reception of CO: lessons from the liver.
Carbon monoxide (CO) is synthesized in vivo by heme oxygenase. Although for many years CO had been regarded as potentially toxic waste, recent studies have indicated that it is a signaling molecule with important physiological functions. Nitric oxide (NO), another diatomic diffusible gas, is regarded as an established signaling molecule. Structural similarities between CO and NO have led many investigators to draw analogies between the two gaseous mediators. Whereas the NO signaling system has been well defined as to its receptor molecule, soluble guanylate cyclase, the CO system has been conceived to require further tuning with respect to identifying its receptor molecules and its downstream effectors. Furthermore, there has been little quantitative information to argue for a physiological role of CO in vivo. This review, therefore, focuses on recent developments on both physiologic and pathophysiologic roles of CO in the model of isolated perfused liver of rats where endogenous production of CO is actually estimated. This model has revealed that CO acts as an endogenous vasorelaxant in the liver and that effects of CO are at least in part cyclic GMP-dependent. It has also provided answers to many questions of hepatobiliary functions that had not been resolved because of the complexity introduced by the interplay between NO and CO.
Kajimura
Mayumi
M
Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, Tokyo 1608582, Japan.
Goda
Nobuhito
N
Suematsu
Makoto
M
D000818:Animals; D001646:Bile / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism
D014665:Vasodilator Agents; D009569:Nitric Oxide; D002248:Carbon Monoxide; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D006162:Guanylate Cyclase; D006152:Cyclic GMP