Proteolytic processing, axonal transport and differential distribution of chromogranins A and B, and secretogranin II (secretoneurin) in rat sciatic nerve and spinal cord

The chromogranin family comprises chromogranin A and B, and secretogranin I I. The present study has focused on the axonal transport of chromogranins/s ecretogranin II and their detailed distribution in peripheral nerves and th e spinal cord. With radioimmunoassay (RIA) and column chromatography, we fi rst studied the processing of chromogranin B and secretogranin II during ax onal transport. No larger precursors of these peptides were detected in the sciatic nerves, indicating that they are already processed to a high degre e early during axonal transport. We also analysed nerve segments above and below a crush, using RIA, in order to compare these accumulation data with those obtained by the cytofluorimetric-scanning (CFS) technique. For the la tter technique, the amounts of accumulation distal to the crush (presumably representing recycling and retrogradely transported peptides) were 30-40% of the amounts in the proximal accumulation for chromogranin A and secreton eurin, in contrast to chromogranin B, which showed 15% recycling. With the RIB, the corresponding values for secretoneurin and PE-11 (antibody against chromogranin B) were 42% and 14%, respectively. Therefore, the data obtain ed by CFS were in excellent agreement with those obtained by RIA. In crushe d sciatic nerves, chromogranin A was present in large axons as well as in s mall- and medium-sized axons. Chromogranin B was mainly restricted to large axons, while secretoneurin was localized to bundles of small axons. This d ifferential distribution was also found in the spinal roots and in the peri pheral terminals. Chromogranin a was present in both ventral and dorsal roo ts, and chromogranin B was detected in ventral roots and in large sensory a xons in the dorsal roots. Secretoneurin was dominant in the dorsal root. Do uble-labelling studies with antibodies against choline acetyltransferase/ve sicular acetylcholine transporter, or against tyrosine hydroxylase, confirm ed that chromogranin a was distributed in cholinergic, sensory, as well as adrenergic neurons. Chromogranin B was mainly present in cholinergic motor neurons and large sensory neurons, and secretoneurin was restricted to adre nergic and sensory neurons. The present study demonstrates that chromograni ns a and B, and secretoneurin are transported with fast axonal transport in the peripheral nerves, with different amounts of recycling, and that they are differentially distributed in different types of neurons in the periphe ral nervous system and the spinal cord, suggesting that each of them may pl ay a special role in subsets of neurons.