PHOTOLYSIS OF A PROTECTING GROUP FOR THE CARBOXYL FUNCTION OF NEUROTRANSMITTERS WITHIN 3-MU-S AND WITH PRODUCT QUANTUM YIELD OF 0.2

The synthesis of a photosensitive blocking group for the carboxyl func tion of neurotransmitters, in this case glycine, is reported. The comp ound, 2-methoxy-5-nitrophenyl glycine ester (caged glycine), is photol yzed by a laser pulse at 308 or 337 nm within 3 mus and with a product quantum yield of 0.2. The compound is hydrolyzed in water with a time constant tau of 6.1 min at pH 7.1 and 3 hr at pH 4.0. Mouse cerebral cortical neurons containing glycine receptors were used in biological assays. A cell-flow device, in which solutions of caged glycine at pH 4.0 were mixed with buffer to give a final pH of 7.1, was used to equi librate the compound pith receptors on the cell surface. Neither the c aged compound nor the 2-methoxy-5-nitrophenol photolysis product affec ted the glycine receptors or modified their response to glycine. When cells equilibrated with caged glycine are irradiated by a laser pulse at 337 nm, glycine receptor channels are opened, as detected in whole- cell current recordings. The approach described may be used in the syn thesis and characterization of photolabile precursors of neurotransmit ters and other compounds that contain carboxyl groups and for kinetic investigations of neurotransmitter receptors in central nervous system cells in the microsecond time domain.