Similarly, the NO depletion in CIS-induced brains could be explained by the potential of CIS to inhibit neuronal nitric oxide synthase (nNOS) “NO-producing enzyme” that is Ca2+/calmodulin-dependent; CIS interacts with Ca2+-binding sites of gastric calmodulin and results in indirect suppression of nNOS activity (Jarve and Aggarwal 1997). The gene discussed is NOS1; the disease is in situ carcinoma.