SPECIFIC MOLECULAR-MASS DETECTION OF ENDOGENOUSLY RELEASED NEUROPEPTIDES USING IN-VIVO MICRODIALYSIS MASS SPECTROMETRY

The specific molecular detection of the endogenous neuropeptides methi onine ([Met](5)) enkephalin and neurotensin released in vivo in rat br ain has been accomplished using microdialysis and mass spectrometry. M icrodialysis probes were implanted in specific brain regions and were used to collect samples from brain extracellular fluids in unanestheti zed, freely moving animals. Microelectrospray/tandem mass spectrometry was used-to achieve molecular-specific identification of the neuropep tides with a sensitivity in the amol/mu l range. Measurements of the a mounts; of neuropeptides in the dialysates obtained from studies of KC l-stimulated release showed that [Met](5)-enkephalin from the globus p allidus/ventral pallidum region was present at a level of approximatel y 4-6 fmol/10 mu l of dialysate and neurotensin from the hypothalamus of approximately 500 amol in 10 mu l of dialysate. In this manuscript, we present the first data of a mass- and molecular-specific detection and quantitation of individual neuropeptides released in response to either intracerebrally or systemically administered compounds.