Evidence for this includes the blockade of stroke damage by inhibitors of NO synthase and a lesser amount of stroke damage in the brains of mice lacking the neuronal form of NO synthase. CO is formed by the action of the enzyme heme oxygenase, which cleaves the heme ring liberating CO and forming biliverdin, which is converted to bilirubin. Just as NO, formed in the endothelial layer of blood vessels, diffuses to the smooth muscle and is a major normal relaxing element of blood vessels, CO is formed by heme oxygenase in the endothelium and also relaxes blood vessels. Besides forming CO, heme oxygenase action gives rise to ferrous iron and biliverdin which is rapidly reduced to bilirubin. We have shown that bilirubin is a key neuronal antioxidant neuroprotectant.
Heme oxygenase facilitates the transport of toxic ferrous ion out of cells.
NMDA receptors had been thought to be co-activated by the amino acids glycine and glutamate. D-Serine appears to be the normal stimulus for the glycine site of this receptor. We isolated IP3 receptor proteins and showed that they possess both the recognition site for IP3 and the associated ion channel whereby IP3 releases intracellular calcium. More recently we have characterized novel intracellular second messengers, the immunophilins. These are a family of proteins first identified as mediators of actions of immunosuppressant drugs such as cyclosporin A and FK506.