Naturally occurring neuronal NO-synthase inactivators found in Nicotiana tabacum (Solanaceae) and other plants

NO-synthase (NOS) is a heme-containing enzyme that catalyzes the oxidation of l-arginine to nitric oxide, an important cellular signaling molecule. Recently, it was found that aqueous extracts of tobacco cigarettes cause the inactivation of the neuronal isoform of NOS (nNOS) and that this may explain some of the toxicological effects of smoking. Although the exact identity of the chemical inactivator(s) is not known, we wondered if extracts prepared from other plants, including those closely related to tobacco, Nicotiana tabacum (Solanaceae), would similarly inactivate nNOS. We examined 33 plants, representing diverse members of the plant kingdom ranging from whisk fern, Psilotum nudum (Psilotaceae) to tobacco and discovered 18 plants that contain a chemical inactivator(s) of nNOS. Of these plants, 16 are members of the core asterids flowering plant group. Of these asterids, 6 are members of the Solanaceae family, of which tobacco is a member. Based on the phylogenetic relationship of the plants, it is possible that the same chemical or related chemical inactivator(s) exist. This, in turn, may help elucidate the structure of the chemical(s), as well as provide a source of a potentially novel inactivator of nNOS. The alkaloid nicotine can be excluded as putative nNOS inhibitor.