Pig splenic nerve: peptides derived from chromogranins by proteolytic processing during axonal transport

We have investigated the proteolytic processing of chromogranin A, chromogr anin B and NESP55 (a novel chromogranin-like protein) during axonal transpo rt using pig splenic nerve as a model. We have also studied the presence of chromogranin-derived peptides in the perfusate during electrical stimulati on of this nerve. High-performance gel filtration chromatography followed b y radioimmunoassay (RLA) revealed that chromogranins are proteolytically pr ocessed to varying degrees during axonal transport. For chromogranin A and NESP55, the precursor is still present in the proximal part of the nerve, w hereas in the distal part and nerve terminals, intermediate-sized peptides and the free peptides GE-25 and GAIPLRRH dominate, respectively. For chromo granin B, the precursor has already been processed to an intermediate-sized peptide in the proximal part of the nerve, which is also present in the di stal parts together with the free peptide PE-11. For chromogranin B and NES P55, only the free peptides PE-11 and GAIPIRRH, or in the case of chromogra nin A, the free peptide GE-25 plus an intermediate-sized one, are released from the terminals into the splenic perfusate. These results demonstrate th at chromogranins are processed to smaller peptides during axonal transport. (C) 1999 Elsevier Science B.V. All rights reserved.