PROCESSING OF PRODYNORPHIN-DERIVED PEPTIDES IN STRIATAL EXTRACTS - IDENTIFICATION BY ELECTROSPRAY-IONIZATION MASS-SPECTROMETRY LINKED TO SIZE-EXCLUSION CHROMATOGRAPHY

Proteolytic processing of prodynorphin-derived peptides in rat brain w as studied with the help of high performance size exclusion chromatogr aphy (SEC) connected to electrospray ionization mass spectrometry. Ext racts from rat striatum were incubated with individual synthetic dynor phin peptides. Dynorphin A was the most resistant to proteolytic cleav age, converting slowly to Leu-enkephalin (0.3 pmol/min), whereas dynor phin B was processed to this pentapeptide at a 10(4)-fold higher rate. Minor cleavage was also observed between Arg(6) - Arg(7). Alphaneoend orphin was also rapidly metabolized to Leu-enkephalin (6 nmol/min) and , to a lesser extent, to Leu-enkephalinArg(6). This new strategy for s tudying peptidases can easily be adapted to identification of componen ts present in body fluids.