SYNTHESIS AND PHOTOCHEMISTRY OF PHOTOLABILE DERIVATIVES OF GAMMA-AMINOBUTYRIC-ACID FOR CHEMICAL KINETIC INVESTIGATIONS OF THE GAMMA-AMINOBUTYRIC-ACID RECEPTOR IN THE MILLISECOND TIME REGION

The gamma-aminobutyric acid (GABA) receptor is an abundant neuronal re ceptor in the mammalian and invertebrate nervous systems and is associ ated with an inhibitory chloride ion channel. GABA is the endogenous n eurotransmitter for the receptor and can trigger both fast activation and a reversible desensitization of the receptor. A series of photolab ile amine-linked o-nitrobenzyl derivatives of GABA were synthesized th at photolyze rapidly to release free GABA. The photochemical propertie s of the GABA precursors were determined; the compounds undergo rapid photolysis, initiated with UV irradiation at 308 nm, and release free GABA on a millisecond time scale. The pH of the photolysis medium affe cts both the quantum yield and the rate of photolysis. For example, th e quantum yield observed for N-(alpha-carboxy-2-nitrobenzyl)-gamma-ami nobutyric acid increases from 0.06 at pH 5.0 to 0.1 at pH 10.5, and th e half-life for the photolytic reaction decreases from 1.0 to 2.5 ms i n the same pH range. Photolysis of the compounds induces rapid onset o f transmembrane ion currents in mouse cortical neurons. The potential of the new compounds for use in rapid chemical kinetic investigations of the neuronal GABA receptor is demonstrated.