Doraiswamy Ramesh

Chemical Kinetic Investigations of the Channel-Opening Process of Neurotransmitter Receptors

The application of chemical kinetic investigations, using fast reaction techniques, to the studies of neuronal receptor-mediated reactions has been recently reported (Hess et al., 1979, 1987). However, the use of such mixing techniques is limited to the studies of receptors in membrane vesicles (Hess et al., 1979) with a time resolution of 5 msec, or to measurements with receptor-containing cells (Udgaonkar and Hess, 1987) with a 20 msec time resolution. In order to clarify the activation process of receptors, a new method which has a faster time resolution must be developed. Caged compounds pioneered by Professor Jack Kaplan, University of Pennsylvania, and Professor David Trentham, National Institute for Medical Research, London, are good candidates for this purpose. In contrast to their oxygen-bonded caged compounds, we protected nitrogen atoms included in many neurotransmitters. We have synthesized caged neurotransmitters bonded to a photo-dissociative o-nitrobenzyl group with the nitrogen atom. These compounds have shown relatively fast photolysis and have been useful for the study of neuronal receptors.