Acetylcholinesterase hydrolyses chromogranin a to yield low molecular weight peptides

Abstract

The major soluble protein of bovine chromaffin granules chromogranin A was purified by reverse-phase high performance liquid chromatography. Brief incubations with either acetylcholinesterase or trypsin cleaved chromogranin A to yield two chromogranin-immunoreactive polypeptides which were similar in molecular weight to two of the major endogenous chromogranin polypeptides. A number of peptidase inhibitors which strongly inhibited tryptic digestion of chromogranin A also inhibited the acetylcholinesterase digestion, although they were less potent. More prolonged digestion of chromogranin A with acetylcholinesterase produced a large number of peptides which were similar to some of the endogenous chromogranin peptides in their elution profile by high performance liquid chromatography. In contrast, complete tryptic digestion of chromogranin A yielded peptides with a totally different elution profile. The experiments indicate that acetylcholinesterase possesses a peptidase activity which is similar, but not identical to trypsin, and suggest that a second non-tryptic activity is also present. They also suggest that acetylcholinesterase, an enzyme found in chromaffin cells, may process chromogranin A to yield lower molecular weight chromogranins in bovine chromaffin cells.