MOLECULAR CHARACTERIZATION OF IMMUNOREACTIVITIES OF PEPTIDES DERIVED FROM CHROMOGRANIN-A (GE-25) AND FROM SECRETOGRANIN-II (SECRETONEURIN) IN HUMAN AND BOVINE CEREBROSPINAL-FLUID

Chromogranin A and secretogranin II are members of the so-called chrom ogranins, the acidic proteins stored in neuroendocrine large dense-cor e vesicles. We characterized chromogranin A and secretogranin II immun oreactivities in cerebrospinal fluid by radioimmunoassays using synthe tic peptides derived from these components (GE-25 for chromogranin A a nd secretoneurin for secretogranin II), In lumbar cerebrospinal fluid, high levels (more than 1000 fmol/ml) of these two components were fou nd, whereas in ventricular cerebrospinal fluid the secretoneurin level s were relatively low. The cerebrospinal fluid/serum ratio for secreto neurin was close to 170. High-performance liquid chromatography reveal ed that in both cerebrospinal fluid and extracts from human brain secr etoneurin was the predominant immunoreactive component. In cerebrospin al fluid chromogranin A immunoreactivity was present as intermediate-s ized peptides with little intact chromogranin A and free GE-25 peptide . In human brain samples smaller peptides including GE-25 were more pr edominant. Analogous findings For secretoneurin and chromogranin A wer e obtained for bovine brain samples. We can conclude that chromogranin s are present in cerebrospinal fluid in concentrations much higher tha n those of classical neuropeptides also stored in large dense-core ves icles. Therefore, their degree of proteolytic processing can be analys ed with small samples of cerebrospinal fluid. A possible disturbance o f proteolytic processing in large dense-core vesicles in various patho logical conditions can now be discovered.