Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1

“…All HO isoforms are inhibited by the metallo-protoporphyrins zinc protoporphyrin IX (ZnPP IX) and tin protoporphyrin IX (SnPP IX). HO is expressed in many types of cells, including VSMCs [6] . HO-1, also known as heat shock protein 32, is ubiquitously distributed and highly inducible by a variety of physiological and pathophysiological stimuli [7] .…”

Chemoreception in the context of the general biology of ROS

“…Through its interaction with guanylate cyclase it produces an increase in cGMP and thereby it behaves alike NO • , i.e., NO • and CO are physiological endothelial-derived relaxing factors for blood vessels in most vascular beds, both seem to act as neurotransmitters or cotransmitters in central and peripheral nervous system and both participate in smooth muscle relaxation in the gastrointestinal tract (Sanders and Koh, 2006). But it should be kept in mind that NO • is very reactive and that RNS are toxic, while CO as stated above is unreactive and it is disposed throughout its binding to hemoglobin and elimination in the respiratory system (although apparently a minor proportion can be oxidized to CO 2 by cytochrome oxidase; Wu and Wang, 2005). However, the dilating actions of CO (and NO • ) are not solely due to activation of guanylate cyclases and the subsequent transduction cascade (Ryter et al, 2006) can also be directly produced by their direct interactions with ion channels, particularly with maxi-K channels.…”

“…Recently, working with rat CB, we have found immunocytochemically both HO isoforms in tyrosine hydroxylase positive chemoreceptor cells, and additionally that HO-2 is transcribed at a very slow rate in comparison to HO-1 (based on the threshold cycle for each gen in relative quantification studies in our qPCR system; Caceres, Rocher and Gonzalez, unpublished). Finally, variable effects of CO on Ca 2+ currents mediated by soluble guanylate cyclase have also been described (see Wu and Wang, 2005).…”

“…In the rat tail artery it was shown that part of the relaxation in phenylephrine precontracted strips produced by CO was endothelium independent and sensitive to charibdotoxin implying that it was due to maxi-K activation (see Wu and Wang, 2005). The same authors working with isolated smooth muscle cells of the same tail artery preparation showed in inside-out patches that CO increased the opening probability of maxi-K, and by chemically manipulating histidine residues in the external surface of the membrane, the authors concluded that CO interacted directly with histidine residues of the maxi-K channel protein (see Wu and Wang, 2005). In additional experiments using full pharmacological activation of maxi-K regulatory ␤ subunits and transfection of maxi-K ␣ subunits in HEK cells the authors concluded that the regulatory subunits were not necessary to obtain the stimulatory effect of CO (see Wu and Wang, 2005).…”

“…The same authors working with isolated smooth muscle cells of the same tail artery preparation showed in inside-out patches that CO increased the opening probability of maxi-K, and by chemically manipulating histidine residues in the external surface of the membrane, the authors concluded that CO interacted directly with histidine residues of the maxi-K channel protein (see Wu and Wang, 2005). In additional experiments using full pharmacological activation of maxi-K regulatory ␤ subunits and transfection of maxi-K ␣ subunits in HEK cells the authors concluded that the regulatory subunits were not necessary to obtain the stimulatory effect of CO (see Wu and Wang, 2005). Comparable results have been obtained by Xi et al (2004) in native and cotransfected channels, finding additionally that CO shifted to the left the Ca + -dependent activation of maxi-K channel ␣ subunits.…”