Biosynthesis, axonal transport and turnover of neuronal substance P.

In dorsal root ganglia substance P is synthesized ribosomally, probably via a precursor. A second peptide, apparently a modified form of substance P (8-11), is cosynthesized with substance P and transported with it down both dorsal roots and peripheral branches. Four times as much substance P-like immunoreactivity is transported peripherally as centrally. Only 30% of axonal substance P-like immunoreactivity is available for rapid axonal transport and this is transported at a rate of 4.9 mm h-1. Axonal transport is not necessary for substance P synthesis. Doses of anisomycin which inhibit CNS protein synthesis by more than 95% do not cause any fall in substance P levels over an eight-hour period in ganglia, spinal cord or brain, suggesting that turnover is slower than that of conventional transmitters. However, stimulation of the hindlimbs of these animals reduces substance P levels in the dorsal horn. The turnover rate of spinal cord substance P, estimated either by relating the amount transported down dorsal roots to that in terminals or by measuring the decline of substance P levels after intrathecal colchicine, is four to five days. The functional organization of the substance P neuron is discussed with particular reference to the maintenance of peptide levels in terminals.