Nitric oxide and experimental epilepsy

Abstract

In 1987, it was revealed that endothelium-derived relaxing factor (EDRF) and nitric oxide (NO) are the same molecule. One year later, it was reported that stimulation of cultured cerebellar cells with the glutamate receptor agonist N-methyl-D-aspartate (NMDA) induced an elevation of cyclic guanosine 3-5 monophosphate (cGMP) levels, which was associated with the release of nitric oxide. 1992 was announced as the 'year of NO' by the Editorial Board of Science. In 1995, 3178 papers including the term 'nitric oxide' were indexed in Medline, while the number was only 85 in 1988. NO is a reactive free radical gas that has neither storage sites nor release mechanisms. It has a half-life of less than 5 second under normal physiological conditions. In the brain, NO is produced via conversion of the amino acid L-arginine into L-citrulline. These reactions are catalysed by the enzyme, nitric oxide synthase (NOS) and various cofactors. In the target cells, NO activates soluble guanylate cyclase to increase the cGMP level or interact with other heme containing proteins. NO, which is accepted as a transsynaptic retrograde messenger, is an important molecule in many physiological and pathophysiological states. In this review, we discuss only the evidence that NO is involved in epileptiform activity. While NO was envisaged as endogenous convulsant, a growing body of evidence demonstrates that this molecule is also anticonvulsant. Our own results demonstrated that NO might be an endogenous anticonvulsant substance. As a conclusion, small-gaseous messenger molecules such as NO should be taken into consideration for a better understanding and an easier treatment of epilepsy and many other diseases related to central nervous system.