 |
| | |
| Elevated Nitric Oxide/Peroxynitrite Theory of Multiple Chemical Sensitivity: Central Role of N-Methyl-d-Aspartate Receptors in the Sensitivity Mechanism Martin L. Pall School of Molecular Biosciences, Washington State University, Pullman, Washington, USA Abstract
The elevated nitric oxide/peroxynitrite and the neural sensitization theories of multiple chemical sensitivity (MCS) are extended here to propose a central mechanism for the exquisite sensitivity to organic solvents apparently induced by previous chemical exposure in MCS. This mechanism is centered on the activation of N-methyl-d-aspartate (NMDA) receptors by organic solvents producing elevated nitric oxide and peroxynitrite, leading in turn to increased stimulating of and hypersensitivity of NMDA receptors. In this way, organic solvent exposure may produce progressive sensitivity to organic solvents. Pesticides such as organophosphates and carbamates may act via muscarinic stimulation to produce a similar biochemical and sensitivity response. Accessory mechanisms of sensitivity may involve both increased blood-brain barrier permeability, induced by peroxynitrite, and cytochrome P450 inhibition by nitric oxide. The NMDA hyperactivity/hypersensitivity and excessive nitric oxide/peroxynitrite view of MCS provides answers to many of the most puzzling aspects of MCS while building on previous studies and views of this condition. Key words: excitatory neurotransmitters, glutamate, long-term potentiation, muscarinic, organic solvents, oxidative stress, reactive nitrogen species, retrograde messenger, synaptic transmission. Environ Health Perspect 111:1461-1464 (2003) . doi:10.1289/ehp.5935 available via http://dx.doi.org/ [Online 9 April 2003]
The full version of this article is available for free in HTML or PDF formats. |
|
|
|
|
